lactoferrin and Inflammatory-Bowel-Diseases

Lactoferrin (LF), a glycoprotein found in mucosal secretions, is characterized by a wide range of functions, including immunomodulatory and anti-inflammatory activities. Moreover, several investigations confirmed that LF displays high effectiveness against multiple bacteria and viruses and may be regarded as a potential inhibitor of enveloped viruses, such as presently prevailing SARS-CoV-2. In our review, we discuss available studies about LF functions and bioavailability of different LF forms in in vitro and in vivo models. Moreover, we characterize the potential benefits and side effects of LF use; we also briefly summarize the latest clinical trials examining LF application. Finally, we point potential role of LF in inflammatory bowel disease and indicate its use as a marker for disease severity.

Topics: Anti-Infective Agents; Humans; Immunomodulating Agents; Inflammatory Bowel Diseases; Lactoferrin; SARS-CoV-2

Lactoferrin (LF) is one of the major functional proteins in maintaining human health due to its antioxidant, antibacterial, antiviral, and anti-inflammatory activities. Abnormal levels of LF in the human body are related to some serious diseases, such as inflammatory bowel disease, Alzheimer's disease and dry eye disease. Recent studies indicate that LF can be used as a biomarker for diagnosis of these diseases. Many methods have been developed to detect the level of LF. In this review, the biofunctions of LF and its potential to work as a biomarker are introduced. In addition, the current methods of detecting lactoferrin have been presented and discussed. We hope that this review will inspire efforts in the development of new sensing systems for LF detection.

Topics: Alzheimer Disease; Animals; Biomarkers; Biosensing Techniques; Chromatography; Dry Eye Syndromes; Electrophoresis, Capillary; Feces; Humans; Immunoassay; Inflammatory Bowel Diseases; Lactoferrin; Predictive Value of Tests; Saliva; Tears

Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD) patients. Therefore, monitoring of IBD activity can avoid the poor prognosis. Serum biomarkers reflect a summation of systemic host responses rather than being specific for intestinal inflammation. And endoscopic monitoring is invasive, costly, and time consuming. The objective of our study was to perform a meta-analysis evaluating the diagnostic accuracy of fecal lactoferrin (FL) in assessing IBD activity.. We systematically searched the databases from inception to May 2018 that evaluated IBD activity. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio.. Ten studies comprising 773 IBD patients were included in the meta-analysis. The pooled sensitivity and specificity values for assessing ulcerative colitis (UC) activity were 0.81 [95% confidence interval (CI), 0.64-0.92] and 0.82 (95% CI, 0.61-0.93), respectively. And the pooled sensitivity and specificity values for assessing Crohn's disease (CD) activity were 0.82 (95% CI, 0.73-0.88) and 0.71 (95% CI, 0.63-0.78), respectively. The diagnostic performance of the FL assay in the UC patients appeared to be superior to that in the CD patients.. Our meta-analysis has found that FL is an inexpensive, simple, stable, and useful screening marker with high sensitivity and modest specificity for assessing IBD activity, appearing to have greater ability to evaluate UC rather than CD.

Topics: Biomarkers; Colitis, Ulcerative; Crohn Disease; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin

Irritable bowel syndrome (IBS) is among the most commonly encountered conditions in primary care and gastroenterology. There is ample evidence that an IBS diagnosis based on symptom-based criteria and exclusion of alarm features that would otherwise support diagnostic testing is accurate and durable. For many clinicians, however, IBS remains a diagnosis of exclusion because of concern surrounding missed diagnoses of inflammatory bowel disease (IBD) or other organic gastrointestinal diseases. Using blood and/or fecal biomarker tests to shift the precolonoscopy probability of IBD in patients with symptoms mimicking IBS is becoming an increasingly reasonable practice with improvement in 'preliminary' tests.. Fecal calprotectin (FCP) testing appears to be the most sensitive preliminary test for discriminating IBD from IBS. Although both fecal lactoferrin and FCP were superior to serum C-reactive peptide (CRP) in their diagnostic accuracy, FCP is superior to fecal lactoferrin based on available literature.. In patients with IBS with diarrhea who have not undergone previous extensive evaluation, the ability of screening tests to detect colonic inflammation is improving. FCP and fecal lactoferrin are reliable predictors of colonic inflammation and should be considered for standard testing in patients with IBS-D symptoms to help identify those who would benefit most from colonoscopy. Although predictive, there currently are no fecal or serum tests that can definitively identify or subtype IBD.

Topics: Biomarkers; C-Reactive Protein; Diagnosis, Differential; Endoscopy, Gastrointestinal; Feces; Humans; Inflammation; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte L1 Antigen Complex; Reproducibility of Results

Crohn's disease and ulcerative colitis are heterogeneous inflammatory bowel diseases, and therapeutic requirements vary among patients. We have a limited capacity to predict disease progression for individual patients, therefore it is important that they are evaluated for the presence of active disease when symptoms are mild or even absent, when patients are more likely to respond to new treatment interventions. It then is important to monitor responses to treatment, to quickly identify those therapies that are ineffective, modify or change therapy, and avoid disease complications. Studies are underway to assess the effects of different monitoring strategies. Because of the heavy burden of severe inflammatory bowel disease on patients' health and quality of life, and the association between intestinal healing and disease progression in high-risk patients, a treat-to-target strategy (based on tissue healing) is likely to be optimal.

Topics: Biomarkers; C-Reactive Protein; Endoscopy, Digestive System; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Ultrasonography

Patients with diagnosed inflammatory bowel disease (IBD) will commonly experience a clinical relapse in spite of a prolonged therapy-induced period of clinical remission. The current methods of assessing subclinical levels of low-grade inflammation which predispose patients to relapse are not optimal when considering both cost and patient comfort. Over the past few decades, much investigation has discovered that proteins such as calprotectin that are released from inflammatory cells are capable of indicating disease activity. Along with C-reactive protein and erythrocyte sedimentation rate, calprotectin has now become part of the current methodology for assessing IBD activity. More recently, research has identified that other fecal and serum biomarkers such as lactoferrin, S100A12, GM-CSF autoantibodies, α1-antitrypsin, eosinophil-derived proteins, and cytokine concentrations have variable degrees of utility in monitoring gastrointestinal tract inflammation. In order to provide direction toward novel methods of predicting relapse in IBD, we provide an up-to-date review of these biomarkers and their potential utility in the prediction of clinical relapse, given their observed activities during various stages of clinical remission.

Topics: alpha 1-Antitrypsin; Biomarkers; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Predictive Value of Tests; Recurrence; S100A12 Protein

The diagnosis and monitoring of inflammatory bowel disease (IBD) has traditionally relied on clinical assessment, serum markers of inflammation and endoscopic examination. Fecal biomarkers such as calprotectin (FC) and lactoferrin (FL) are predominantly derived from neutrophils, are easily detectable in the feces and are now established as valuable markers of intestinal inflammation. In recent years, a 'treat to target' concept has emerged for the management of IBD. Adequate control of inflammation in IBD at a biochemical level is quickly becoming an important target in IBD management.. Fecal biomarkers have been shown to be significantly and consistently increased in both adult and pediatric patients with IBD versus those without IBD. Fecal biomarkers are therefore useful in determining those patients with gastrointestinal symptoms who are likely to benefit from colonoscopy versus those in whom colonoscopy is likely to be normal. Fecal biomarkers correlate significantly with endoscopic disease in both Crohn's disease and ulcerative colitis. Suggested cutoffs for FC for endoscopically active disease in IBD range from 50 to 280 μg/g. Fecal biomarkers reflect the success of treatment intensification and can help predict clinical relapse. Both FC and FL are accurate in the detection of postoperative endoscopic recurrence of Crohn's disease, and FC may be clinically useful in predicting those patients with acute severe ulcerative colitis who may progress to colectomy. There are limitations to these fecal tests including a false positive rate and intra-individual variability.. This review focuses on the role of fecal biomarkers in the diagnosis, monitoring and management of IBD and how best to interpret results. We will discuss the emerging role of these biomarkers in the IBD management landscape including FC-guided drug dosing and the development of home-based testing and e-health applications. Fecal biomarker results must always be interpreted in a clinical context. Endoscopic assessment remains the gold standard for diagnosis and monitoring of IBD.

Topics: Biomarkers; Colonoscopy; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex

Irritable bowel syndrome (IBS) is viewed as a diagnosis of exclusion by most providers. The aim of our study was to perform a systematic review and meta-analysis to evaluate the utility of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin, and fecal lactoferrin to distinguish between patients with IBS and inflammatory bowel disease (IBD) and healthy controls (HCs).. A systematic online database search was performed. Included studies were prospective, adult, diagnostic cohort studies with any of the four tests. The means and s.d. values of biomarker logarithms were estimated based on studies that gave medians and either confidence intervals for the median, interquartile ranges, or ranges. We used a Naive Bayes approach to estimate the probability of being a HC, having IBS, or having IBD based on the biomarker values.. Systematic review identified 1,252 citations. After cross-referencing medical subject headings, detailed evaluation identified 140 potentially relevant journal articles/abstracts for CRP, ESR, calprotectin, and lactoferrin of which 4, 4, 8, and 2 fulfilled our inclusion criteria, respectively. None of the biomarkers reliably distinguished between IBS and healthy controls. At a CRP level of ≤0.5 or calprotectin level of ≤40 μg/g, there was a ≤1% probability of having IBD. Individual analysis of ESR and lactoferrin had little clinical utility.. CRP and calprotectin of ≤0.5 or 40, respectively, essentially excludes IBD in patients with IBS symptoms. The addition of CRP and calprotectin to symptom-based criteria may improve the confident diagnosis of IBS.

Topics: Adult; Biomarkers; Blood Sedimentation; C-Reactive Protein; Diagnosis, Differential; Feces; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte L1 Antigen Complex; Reproducibility of Results

To do a systematic review using meta-analysis to assess the diagnostic accuracy of fecal lactoferrin (FL) in patients with inflammatory bowel disease (IBD).. We performed a literature review and systematically searched the Medline and EMBASE databases for eligible studies. The quality of the included studies was assessed using the QUADAS tool. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model.. Seven studies, involving 1816 patients, met the inclusion criteria. In all studies, the pooled FL sensitivity and pooled specificity were 0.82 (95% confidence interval [CI]: 0.72, 0.89) and 0.95 (95% CI: 0.88, 0.98), respectively. The positive and negative likelihood ratios were 16.63 and 0.18, respectively. The area under the summary receiver-operating characteristic curve (SROC) was 0.95 (95% CI: 0.93, 0.97), and the diagnostic odds ratio was 90.04 (95% CI: 37.01, 219.02). The pooled FL sensitivity and specificity for Crohn's disease (CD) diagnosis (sensitivity =75%, specificity =100%) was not as good as it was for ulcerative colitis (UC) diagnosis (sensitivity =82%, specificity =100%).. FL, as a noninvasive and screening marker, has a high specificity and a modest specificity during the diagnosis of suspected IBD.

Topics: Biomarkers; Colitis, Ulcerative; Crohn Disease; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Odds Ratio; ROC Curve; Sensitivity and Specificity

In the recent decades the rapid development of the studies on new methods used in diagnosis, differential diagnosis, and monitoring the treatment of inflammatory bowel diseases has been observed. To the diagnostics of gastrointestinal disorders new methods such as endoscopic capsule and imaging methods including magnetic resonance have been introduced. Markers of inflammation detected in stool play significant role in the diagnostics. To the best known belong calprotectine and lactoferrin, which are produced by neutral granulocytes. In the present review we have presented the clinical usefulness of detection in the stool of calprotectin, lectoferrin, S100A12 protein and pyruvate kinase. Clinical usefulness of these markers were used in diagnosis, assessment of the treatment results, disease relapse and mucosal healing in inflammatory bowel disease. Determination of fecal calprotectin and lactoferrin in the process of mucosal healing in ulcerative colitis or Crohn's disease are of particular value. Confirmation of these results in multicenter prospective trials will enable in the future to reduce the number of control colonoscopies, which in children are performer under general anesthesia.

Topics: Adolescent; Biomarkers; Capsule Endoscopy; Child; Child, Preschool; Colonoscopy; Diagnostic Imaging; Feces; Humans; Inflammation; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Monitoring, Physiologic; Pyruvate Kinase; S100A12 Protein; Treatment Outcome

To perform a meta-analysis evaluating the diagnostic ability of fecal lactoferrin (FL) to distinguish inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS).. The Medline, EMBASE, Web of Science, Cochrane library and CNKI databases were systematically searched for studies that used FL concentrations to distinguish between IBD and IBS. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model.. Seven studies, involving 1012 patients, were eligible for inclusion. In distinguishing IBD from IBS, FL had a pooled sensitivity of 0.78 (95% confidence interval [CI]: 0.75, 0.82), a specificity of 0.94 (95% CI: 0.91, 0.96), a positive likelihood ratio of 12.31 (95% CI: 5.93, 29.15), and a negative likelihood ratio of 0.23 (95% CI: 0.18, 0.29). The area under the summary receiver-operating characteristic curve was 0.94 (95% CI: 0.90, 0.98) and the diagnostic odds ratio was 52.65 (95% CI: 25.69, 107.91).. FL, as a noninvasive and simple marker, is useful in differentiating between IBD and IBS.

Topics: Biomarkers; Diagnosis, Differential; Feces; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Sensitivity and Specificity

Inflammatory bowel disease is a group of chronic inflammatory conditions of gastrointestinal tract, including ulcerative colitis and Crohn's disease. Diagnosis of inflammatory bowel disease is based on clinical symptoms, lower and/or upper gastrointestinal tract endoscopy with biopsies and histological results. These procedures are invasive for patients and highly expensive. Thus, efforts are underway to establish new noninvasive tests appropriate to diagnosis and management of inflammatory bowel disease. Commonly used, blood markers of inflammation or scales of inflammatory bowel disease activity has been demonstrated to be insufficient. Recently, there has been increasing interest in identifying biomarkers, i.e. calprotectin, lactoferrin, mieloperoxidasis or S100A12 protein in faeces. These proteins are produced by neutrophil granulocytes and clearly reflect inflammation directly in bowel. It should be highlighted that these tests are noninvasive and may be perform repetitiously.

Topics: Biomarkers; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Peroxidase; Sensitivity and Specificity

Crohn's disease (CD), ulcerative colitis (UC), and colitis unclassified, collectively defined as inflammatory bowel disease (IBD), are the consequence of chronic inflammatory reactions in the gastrointestinal tissue. Endoscopy with biopsies is the mainstay in the diagnosis of this inflammation and is also important in the assessment of disease activity and monitoring of treatment. Furthermore, mucosal healing is increasingly becoming a therapeutic target for treatment of IBD and the golden standard of assessing it is endoscopy. However, due to the costs, invasiveness, and to limited endoscopic capacity, the need is strong for reliable surrogate markers of intestinal inflammation. Bowel contents, being in close contact with intestinal mucosa, can take up molecules that are measurable from stool samples and thus can serve as markers of inflammation. The fecal neutrophil-derived biomarkers, especially calprotectin and lactoferrin, have several features of an ideal test for detecting intestinal inflammation: they are noninvasive, simple, and low in cost. The utility of these biomarkers in distinguishing IBD from noninflammatory conditions such as irritable bowel syndrome is well documented. They correlate closely with endoscopic activity both in CD and UC. They allow serial monitoring of disease activity and of treatment success, and can even serve in predicting clinical relapse in unsymptomatic patients or sustained remission after induction with TNF-α-blocking agents. In this review an overview will be given to the role of fecal neutrophil-derived biomarkers calprotectin and lactoferrin in diagnostics and prognostics of IBD.

Topics: Biomarkers; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Neutrophils; Prognosis

Endoscopy has been the gold standard for diagnosing and following patients with inflammatory bowel disease. However, ileocolonoscopy is still an expensive and invasive method. Secondly we do know that clinical scores for ulcerative colitis and Crohn's disease are subjective which creates several problems. And thirdly, when using the known serological markers such as C-reactive protein, white blood cell count en albumin, one should take into account that these markers are not perfect or superior to the current diagnostic techniques given their low sensitivity and specificity. Fecal markers may prove to have a greater specificity. Calprotectin can differentiate between active and inactive inflammatory bowel disease and between inflammatory bowel disease and irritable bowel syndrome. It correlates with the severity of symptoms and it may predict relapse especially in ulcerative colitis. Finally it can be used as a surrogate marker for the endoscopic response during treatment given a normal value of calprotectin is a reliable marker for mucosal healing. Lactoferrin also seems to be a sensitive and specific marker for the detection of chronic inflammation and for predicting relapse. The relationship with the endoscopic activity is significant and lactoferrin values are significantly higher in active endoscopic disease as compared to inactive disease. Finally, given the significant correlation with endoscopic activity, lactoferrin can function as an adequate marker for the monitoring of therapy.

Topics: Biomarkers; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex

Most abdominal disorders present with a limited number of overlapping symptoms. Blood tests are not routinely available for use in diagnosis and so investigation tends to require complex imaging procedures or endoscopy and biopsy. These are invasive for the patient, may be associated with morbidity and mortality and have considerable resource implications. Biochemical tests on a single sample of faeces are therefore a valuable alternative. Measurement of faecal calprotectin has been shown to have a role in the diagnosis of inflammatory bowel disease and in its monitoring. Lactoferrin is also of benefit used in this way. Faecal elastase has been demonstrated to be of use in the diagnosis of pancreatic insufficiency. A number of faecal markers have been explored in colorectal cancer. Faecal occult blood testing is used for population screening, but the metabolomic marker tumour, M2-pyruvate kinase, has potential for use in both diagnosis and screening. DNA testing has advantages in colorectal cancer but the exact applications of such tests require further evaluation.

Topics: Biomarkers; Carcinoma; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Exocrine Pancreatic Insufficiency; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Mass Screening; Metabolome; Occult Blood; Pancreatic Elastase; Pancreatitis; Pyruvate Kinase; Sensitivity and Specificity

The diagnosis and management of inflammatory bowel diseases (IBD), i.e., Crohn's disease and ulcerative colitis, still present a number of challenges. The fecal biomarker lactoferrin has been shown to be useful in the diagnosis and management of these diseases. This review includes a discussion of the current literature on lactoferrin as a biomarker of intestinal disease, detection of disease activity in IBD, comparison of lactoferrin to endoscopy and histology, lactoferrin measurement in pediatric IBD and lactoferrin as a biomarker for monitoring medical treatment in IBD.

Topics: Biomarkers; Endoscopy, Gastrointestinal; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex

Overall, fecal markers have been found to be more accurate than serum markers. However, fecal markers are not specific for IBD and may be elevated in a range of organic conditions. Fecal calprotectin and lactoferrin can still differentiate inflammatory disease from functional bowel disorders. Comparison studies have found an overall diagnostic accuracy in IBD of 80% to 100% for both calprotectin and lactoferrin. Elevated levels are found in both CD and UC making it difficult to distinguish between these 2 diagnoses from these biomarkers alone. Both markers correlated well to mucosal healing and histologic improvement. Hence, they may be useful in monitoring response to treatment and predicting endoscopic and clinical relapse. Overall, patients with elevated markers were at higher risk of postoperative recurrence than those with normal levels. Fecal markers are useful in predicting pouchitis as well. Fecal markers are helpful as an adjunctive tool in overall evaluation of patients with nonspecific symptoms and as a management tool in those with inflammatory disease to monitor disease activity and possibility of relapse. They are less invasive than colonoscopy and can help guide management in a more cost-effective manner.

Topics: Biomarkers; Diagnosis, Differential; Feces; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte L1 Antigen Complex; Predictive Value of Tests; Prognosis; Severity of Illness Index

Inflammatory bowel disease (IBD) encompasses several chronic inflammatory disorders leading to the damage of the gastrointestinal tract. The 2 principal forms of these disorders are ulcerative colitis (UC) and Crohn's disease (CD). Bacteria are involved in the etiology of IBD. Many microorganisms have been put forward as causative factors in IBD, but the primary etiologic agents are still not known. The underlying genetic, environmental, and lifestyle issues can affect the individual's predisposition to these diseases. Immune factors identified in IBD are: dysregulation of the innate and adaptive immune system directed against luminal bacteria or their products found in the intestinal lumen and inappropriate immune responses to organisms in the intestine that normally do not elicit a response, possibly because of intrinsic alterations in mucosal barrier function. However, recent advances in basic science research revealed new insights into the role of specific immune cells and their mediators in intestinal inflammation. The inflammatory mediators known as "inflammasome" are a consequence of the metabolic products (metabolom) of cells and commensal or pathogenic bacteria. Elucidation of inflammasome and metabolom has led to the development of biomarkers specific for each disease that are involved into management strategies targeted at altering specific pathogenic mechanisms that have the potential to modify or change the natural course of these disease entities. The review discusses the potential role of biomarkers in monitoring the inflammasome and therefore the severity of intestinal damage. The microbial ecosystem in the human gut in different microhabitats and metabolic niches contribute to the bowel metabolome.In addition, this review will focus on our expanding understanding of microbial factors associated with both the initiation and maintenance of IBD. New insights acquired from murine genetic models of inflammatory bowel disease will also be discussed.

Topics: Animals; Autoantibodies; Biomarkers; Cell Adhesion Molecules; Cytokines; Disease Models, Animal; Humans; Inflammasomes; Inflammatory Bowel Diseases; Lactoferrin; Metabolome; Metagenome; S100 Proteins; Translational Research, Biomedical

Gastrointestinal (GI) symptoms including abdominal pain, bloating and diarrhoea are a relatively common reason for consulting a physician. They may be due to inflammatory bowel disease (inflammatory bowel disease; Crohn's disease, ulcerative colitis and indeterminate colitis), malignancy (colorectal cancer), infectious colitis or irritable bowel syndrome (IBS). Differentiation between these involves the use of clinical, radiological, endoscopic and serological techniques, which are invasive or involve exposure to radiation. Serological markers include C-reactive protein, erythrocyte sedimentation rate and antibodies (perinuclear antineutrophil cytoplasm antibody and anti-Saccharomyces cerevisiae antibody). Faecal markers that can aid in distinguishing inflammatory disorders from non-inflammatory conditions are non-invasive and generally acceptable to the patient. As IBS accounts for up to 50% of cases presenting to the GI clinic and is a diagnosis of exclusion (Rome III criteria), any test that can reliably distinguish IBS from organic disease could speed diagnosis and reduce endoscopy waiting times. Faecal calprotectin, lactoferrin, M2-PK and S100A12 will be reviewed.

Topics: Biomarkers; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Feces; Gastroenteritis; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte L1 Antigen Complex; Practice Guidelines as Topic; Pyruvate Kinase; S100 Proteins; S100A12 Protein

The identification of noninvasive biomarkers is still one of the major issue for gastroenterologists dealing with inflammatory bowel disease patients, due to the chronicity of these conditions and the early onset of symptoms in the majority of cases. Research attention has focused mainly on fecal proteins, especially calprotectin and lactoferrin, and most of the published data are reassuring about their applicability in the diagnosis and monitoring of these patients. However, there are still pending questions regarding the reliability of fecal proteins especially in the era of mucosal healing and biologics.

Topics: Adult; Biomarkers; Child; Child, Preschool; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Prognosis

Among the available fecal biomarkers for the diagnosis and monitoring of inflammatory bowel disease (IBD), only calprotectin and lactoferrin have translated into useful clinical tools. Lactoferrin can be detected using simple and cheap techniques and it has excellent stability in feces over a long period of time. Fecal lactoferrin has a good diagnostic precision for separating organic and functional intestinal disease. However, a negative fecal lactoferrin test should be interpreted merely as the absence of significant neutrophilic intestinal inflammation. The mean sensitivity and specificity of the fecal lactoferrin determination for the diagnosis of IBD is 80% and 82%, respectively. Some studies have suggested a lower accuracy of lactoferrin when compared with calprotectin for the diagnosis of IBD, indicating that more studies on this topic are necessary. A parallel between fecal lactoferrin levels and IBD activity estimated with clinical, endoscopic, and histological parameters has been confirmed. However, this correlation seems to be lower in Crohn's disease than in ulcerative colitis, mainly when Crohn's disease patients with purely ileal disease are considered. Fecal lactoferrin determination may be useful in predicting impending clinical relapse in IBD patients. Fecal lactoferrin may be a helpful noninvasive diagnostic tool for monitoring therapeutic efficacy, mainly on mucosal healing, as a decreasing concentration of lactoferrin can be interpreted as a marker of therapeutic response. Finally, in patients with Crohn's disease who have undergone ileocolonic resection, those with higher lactoferrin fecal levels might be more prone to postsurgical recurrence.

Topics: Biomarkers; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Predictive Value of Tests

Lactoferrin, a major whey protein, is a red iron-binding protein present mainly in external secretions such as breast milk and in polymorphonuclear neutrophils. The presence of lactoferrin in body fluids is proportional to the flux of neutrophils and its assessment can provide a reliable biomarker for inflammation. In gastrointestinal diseases increased fecal lactoferrin is a sensitive and specific surrogate marker for inflammatory bowel diseases in patients with chronic diarrhea and pain, and ascites lactoferrin can also provide a promising and reliable biomarker for bacterial peritonitis. Lactoferrin in pancreatic juice and stone could provide pathophysiological information of protein plug and stone formation in the pancreatic duct. Serum anti-lactoferrin autoantibody might contribute to the clarification of the pathogenetic mechanisms of autoimmune pancreatitis and liver diseases, although its diagnostic and prognostic value appears to be limited. Further studies will be necessary to elucidate the exact details.

Topics: Ascitic Fluid; Autoantibodies; Biomarkers; Calculi; Carrier Proteins; Feces; Gastrointestinal Diseases; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Pancreatic Juice

We reviewed potential fecal biomarkers of inflammatory bowel disease and assessed their utility in a range of clinical applications.. A literature search using PubMed, MEDLINE, and Embase database was performed, locating all language articles on fecal biomarkers, including calprotectin and lactoferrin. The references of these papers were searched manually for further references.. A wide range of fecal biomarkers have been evaluated in the research setting. Only fecal calprotectin and lactoferrin have translated into useful clinical tools. These biomarkers have demonstrated high sensitivity for organic intestinal disease and good correlation with other measures of disease activity in inflammatory bowel disease.. Fecal calprotectin and lactoferrin are useful triage tools to differentiate organic intestinal disorders from functional disorders. They also have a role in monitoring inflammatory bowel disease activity and predicting relapse.

Topics: Biomarkers; Diagnosis, Differential; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex

The role played by the distinct biological markers in chronic inflammatory bowel disease (IBD) remains insufficiently characterized. C-reactive protein (CRP) has a short half-life and consequently it is elevated early after the onset of the inflammatory process and rapidly decreases after its resolution, making it an attractive marker of disease activity. Moreover, this test is inexpensive and easy to perform and is unaffected by medication. While Crohn's disease is associated with a marked CRP response, there is little or no elevation in the synthesis of this protein in ulcerative colitis. Erythrocyte sedimentation rate provides some advantages such as its ease of determination, availability, and reduced cost. Nevertheless, it also has several disadvantages, notably the fact that its concentration depends on age, the presence of anemia, smoking, and the use of certain drugs. Moreover, its utility is limited by its long half life and consequent prolonged latency period after changes in chronic IBD activity. In theory, fecal markers have the advantages of showing greater specificity in the diagnosis of chronic IBD. Several gastrointestinal diseases, including chronic IBD, show greater leukocyte elimination in feces and a close correlation has been described between fecal calprotectin concentration and leukocyte excretion quantified by 111indium. Advantages of this fecal marker are that it can be detected through a simple and inexpensive technique and also shows excellent stability in feces for prolonged periods. Like calprotectin, fecal lactoferrin is also quantified by a simple and inexpensive ELISA method, although there is considerably less experience with this latter marker.

Topics: Adalimumab; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biomarkers; Blood Sedimentation; C-Reactive Protein; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Feces; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Infliximab; Lactoferrin; Leukocyte L1 Antigen Complex; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Treatment Outcome; Tumor Necrosis Factor-alpha

Distinguishing patients with inflammatory bowel disease from those with irritable bowel syndrome can be difficult. A simple and reliable test that detects intestinal inflammation would therefore be very useful in the clinic. If such a test parameter correlated with the intensity of the inflammatory reaction it could also be used to monitor disease activity. Calprotectin, lactoferrin and nitric oxide are produced and released locally in much greater quantities in the inflamed gut than in the noninflamed gut. These compounds can be readily measured in fecal samples (calprotectin and lactoferrin) or directly in the intestinal lumen (nitric oxide gas). Here, we discuss what is known about these markers, how they could be used in clinical practice and how they can complement existing techniques used for the diagnosis and monitoring of inflammatory bowel disease.

Topics: Biomarkers; Feces; Humans; Inflammatory Bowel Diseases; Intestines; Lactoferrin; Leukocyte L1 Antigen Complex; Nitric Oxide

Determination of inflammatory activity is helpful when assessing the efficacy of drugs in therapeutic trials and in facilitating management of individual patients with inflammatory bowel disease (IBD). Faecal parameters have been hypothesized to be more specific than non-faecal measurements in the assessment of intestinal inflammation.. Review of the literature on faecal measurements in IBD.. Leakage of various proteins and leukocyte products into the intestinal lumen can be assessed and quantified in stool specimens and serve as a measurement of inflammatory activity. Several of these faecal parameters are raised in patients with IBD. There is a considerable overlap between patients with active and those with inactive disease, however, and the correlation of the faecal parameters with disease activity indices is often low. The value of alpha1-antitrypsin measurement in faeces in the assessment of intestinal inflammation has been well established. Further studies in patients with IBD are needed to determine whether other faecal parameters, such as lactoferrin, tumour necrosis factor alpha, PMN-elastase, lysozyme, leucocyte esterase, immunoglobulin A, among others, are more accurate or cost-effective than measurement of alpha1-antitrypsin in the stools of such patients.

Topics: alpha 1-Antitrypsin; Clinical Laboratory Techniques; Diagnosis, Differential; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte Elastase; Leukocytes; Muramidase; Reproducibility of Results; Tumor Necrosis Factor-alpha

Iron-deficiency anemia (IDA) is common in children with inflammatory bowel disease (IBD); however, oral iron supplements are commonly associated with poor compliance due to gastrointestinal side effects. We compared the effect of lactoferrin versus oral ferrous sulfate for the treatment of IDA in children with IBD.. Ninety-two IBD children with IDA were included but only 80 children completed the study and they were randomized into two groups: ferrous sulfate group (n = 40) who received ferrous sulfate 6 mg/kg/day for 3 months and lactoferrin group (n = 40) who received lactoferrin 100 mg/day for 3 months. Complete blood count, serum iron, total iron-binding capacity (TIBC), transferrin saturation (TS), serum ferritin, interleukin-6 (IL-6), and hepcidin 25 were measured before and after the treatment.. Hemoglobin (Hb), mean corpuscular volume, serum iron, TS, and serum ferritin significantly increased, while TIBC decreased significantly after the administration of either ferrous sulfate or lactoferrin compared to their baseline data. In addition, lactoferrin significantly increased Hb, serum iron, TS, and serum ferritin compared to ferrous sulfate. Moreover, lactoferrin significantly decreased IL-6 and hepcidin levels.. Lactoferrin is a promising effective treatment with fewer side effects than oral elemental iron in children with IBD and IDA.. The study was registered at www.pactr.org (PACTR202002763901803).. Iron-deficiency anemia (IDA) in children with inflammatory bowel disease (IBD) is treated with oral iron therapy; however, oral iron supplements are commonly associated with poor compliance due to gastrointestinal side effects. To the best of our knowledge, our study was the first in pediatrics that compared the effect of lactoferrin versus oral ferrous sulfate as an iron supplement for the treatment of IDA in children with IBD. We found that lactoferrin is a promising effective treatment with fewer side effects than oral elemental iron in children with IBD and IDA.

Topics: Anemia, Iron-Deficiency; Child; Chronic Disease; Female; Ferritins; Ferrous Compounds; Hemoglobins; Hepcidins; Humans; Inflammatory Bowel Diseases; Interleukin-6; Iron; Lactoferrin; Pregnancy; Pregnancy Complications, Hematologic

There is a keen research upon the effects of nutraceuticals on inflammatory bowel disease. The purpose of this study was to explore the effect of mastiha supplement, rich in bioactive nutraceuticals, in active inflammatory bowel disease. This is a randomised, double-blind, placebo-controlled clinical trial. Α total of 60 inflammatory bowel disease patients were enrolled and randomly allocated to mastiha (2.8 g/day) or placebo groups for 3 months adjunct to stable medical treatment. Medical and dietary history, Inflammatory Bowel Disease Questionnaire (IBDQ), Harvey-Bradshaw index, partial Mayo score, biochemical indices, faecal, and blood inflammatory markers were assessed. A clinically important difference between groups in IBDQ was defined as primary outcome. Inflammatory Bowel Disease Questionnaire score significantly improved in verum compared with baseline (p = 0.004). There was a significant decrease in faecal lysozyme in mastiha patients (p = 0.018) with the mean change being significant (p = 0.021), and significant increases of faecal lactoferrin (p = 0.001) and calprotectin (p = 0.029) in the placebo group. Fibrinogen reduced significantly (p = 0.006) with a significant mean change (p = 0.018), whereas iron increased (p = 0.032) in mastiha arm. Our results show regulation of faecal lysozyme by mastiha supplement adjunctive to pharmacological treatments in active inflammatory bowel disease. An effect secondary to a prebiotic potency is proposed.

Topics: Biomarkers; Dietary Supplements; Double-Blind Method; Feces; Female; Humans; Inflammatory Bowel Diseases; Lactoferrin; Male; Pistacia; Surveys and Questionnaires

Natural products have been studied regarding their effectiveness on Inflammatory Bowel Disease (IBD).. To examine the effects of Mastiha (Pistacia lentiscus var. Chia) on clinical course and amino acid (AA) profile of patients in remission.. This is a randomised, double-blind, placebo-controlled clinical trial.. Patients (n = 68) were randomly allocated to Mastiha (2.8  g/day) or placebo adjunct to stable medication. Free AAs were identified applying Gas Chromatography-Mass Spectrometry in plasma. Medical-dietary history, Inflammatory Bowel Disease Questionnaire, Harvey-Bradshaw Index, Partial Mayo Score, biochemical, faecal and blood inflammatory markers were assessed. Primary endpoint was the clinical relapse rate at 6 months. Secondary endpoints included variations in free AAs, inflammatory biomarkers and quality of life. Statistical significance was set at 0.05.. Concerning AAs and biochemical data, alanine (p = 0.006), valine (p = 0.047), proline (p = 0.022), glutamine (p < 0.001) and tyrosine (p = 0.043) along with total cholesterol (p = 0.032) and LDL cholesterol (p = 0.045) increased only in placebo group compared with baseline and the change between the study groups was significantly different. Inflammatory markers had not a significantly different change between the two groups, even serum IL-6, faecal calprotectin and faecal lactoferrin increased only in the placebo group. Although Mastiha was not proven superior to placebo in remission rate (17.6% vs. 23.5%, p = 0.549), attenuation in increase of free AAs levels in verum group is reported.. Mastiha inhibited an increase in plasma free AAs seen in patients with quiescent IBD. Since change of AAs is considered an early prognostic marker of disease activity, this indicates a potential role of Mastiha in remission maintenance.

Topics: Adolescent; Adult; Aged; Amino Acids; Biomarkers; Double-Blind Method; Feces; Female; Humans; Inflammatory Bowel Diseases; Interleukin-6; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Pistacia; Placebos; Quality of Life; Treatment Outcome

This study was designed to evaluate the accuracy of four different fecal markers in discriminating between irritable bowel syndrome, inflammatory bowel disease, and other forms of colitis and to examine the feasibility of collecting fecal samples in outpatients.. We prospectively included 20 patients with irritable bowel syndrome, 36 with inflammatory bowel disease (24 Crohn's disease, 12 ulcerative colitis), and 18 with other forms of colitis (8 infectious colitis, 5 ischemic colitis, 5 medication-induced colitis). Diagnosis was established by clinical, laboratory, and endoscopic workup. Blinded fecal samples were measured for calprotectin (PhiCal-Test, ELISA), lactoferrin (IBD-SCAN, ELISA), Hexagon OBTI (immunochromatographic test for detection of human hemoglobin), and LEUKO-TEST (lactoferrin latex-agglutination test).. Overall accuracy for discriminating irritable bowel syndrome from inflammatory bowel disease or other forms of colitis was recorded, respectively: IBD-SCAN 91/100 percent, PhiCal-Test 89/100 percent, LEUKO-TEST 83/89 percent, Hexagon OBTI 77/84 percent, C-reactive protein 71/79 percent, and blood leukocytes 63/68 percent. Differentiation of inflammatory bowel disease from other forms of colitis with fecal markers was as follows: range of overall accuracy from 43 to 50 percent. Overall accuracy (in percent) for discrimination of irritable bowel syndrome from patients with Crohn's disease in remission (CDAI<150) was: IBD-SCAN 90, PhiCal-Test 90, LEUKO-TEST 85, Hexagon OBTI 77. Calprotectin and lactoferrin were significantly elevated in patients with Crohn's disease with CDAI>150 compared with those in remission. Fecal sampling feasibility in outpatients was high (acceptance rate 95 percent).. IBD-SCAN and PhiCal-Test have the best overall accuracy for detection of colitis, followed by LEUKO-TEST, Hexagon OBTI, C-reactive protein, and blood leukocytes. Accuracy of fecal markers is high even in patients with Crohn's disease in remission. Fecal sampling feasibility was high in outpatients. Because fecal markers are unspecific, endoscopic workup remains crucial to determine the underlying cause of colitis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Colitis; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Feasibility Studies; Feces; Female; Hemoglobins; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Latex Fixation Tests; Leukocyte L1 Antigen Complex; Male; Middle Aged; Predictive Value of Tests

We investigated which neutrophil-derived proteins in whole gut lavage fluid (WGLF) most accurately reflect disease activity in inflammatory bowel disease.. WGLF was obtained from patients undergoing whole gut lavage as a bowel preparation for colonoscopy. Twenty-seven patients with ulcerative colitis (UC), 23 patients with Crohn's disease (CD), and 35 control subjects were examined. The concentrations of lactoferrin, polymorphonuclear neutrophil elastase (PMN-E), myeloperoxidase, and lysozyme in WGLF were measured by ELISA. For the assessment of stability, WGLF samples were stored at 37 degrees C for various periods.. In UC, the concentrations of lactoferrin, myeloperoxidase, and lysozyme in WGLF had good correlations with colonoscopic grading. Zero, 12, five, and 10 of 28 samples from active UC patients showed normal concentrations of lactoferrin, PMN-E, myeloperoxidase, and lysozyme, respectively. In CD, the concentrations of lactoferrin and myeloperoxidase had good correlations with the Crohn's disease activity index. Thirteen and seven of 36 samples from inactive CD patients (Crohn's disease activity index < or = 150) showed high concentrations of lactoferrin and myeloperoxidase, respectively. Most of them (11/13, 6/7) were found to have ulceration by colonoscopy or small bowel x-ray. The ratio of the lactoferrin concentration in the WGLF supernatant to that in total WGLF was highest among these proteins in all disease groups and control subjects. Lactoferrin and myeloperoxidase showed good stability in WGLF, whereas PMN-E and lysozyme did not.. Lactoferrin is the most suitable of these proteins for use as a neutrophil-derived WGLF marker of intestinal inflammation.

Topics: Adult; Biomarkers; Colonoscopy; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte Elastase; Male; Middle Aged; Muramidase; Neutrophils; Peritoneal Lavage; Peroxidase; Prognosis; Reference Values; Sensitivity and Specificity; Severity of Illness Index

Fecal alpha 1-antitrypsin (alpha 1-AT), alpha 2-macroglobulin (alpha 2-M), lysozyme (Lz), and lactoferrin (Lf) levels were measured in 73 samples from 32 patients with ulcerative colitis (UC), 52 samples from 21 patients with Crohn's disease (CD), and 41 samples from 21 healthy volunteers. According to three degree of bowel activity, the UC patients were divided into 4 groups and the CD patients were divided into 2 groups. Fecal alpha 1-AT levels were measured by latex agglutination and the other protein parameters by ELISA. All protein levels, except alpha 1-AT, rose as the degree of activity increased. The fecal protein markers alpha 2-M, LZ, and Lf had significantly higher positive rates than the serum inflammatory markers and activity index in the moderate and severe UC groups, and alpha 2-M and Lf had significantly higher rates in the CD (+) group. Based on these findings measurement of fecal levels on alpha 2-M, LZ, and Lf appeared to be useful activity markers for UC, and alpha 2-M and Lf for CD.

Topics: Adult; alpha 1-Antitrypsin; alpha-Macroglobulins; Biomarkers; Enzyme-Linked Immunosorbent Assay; Feces; Female; Humans; Inflammatory Bowel Diseases; Lactoferrin; Latex Fixation Tests; Male; Muramidase

The pathogenic importance of antineutrophil cytoplasmic antibodies (ANCAs) in inflammatory bowel disease (IBD) is unclear and target antigen localisation studies may lend insight to the specific pathogenic mechanisms of IBD. In this pilot study, we looked at occurrence of ANCA in Asian IBD patients. In ANCA-positive samples, we analysed for the presence of target antigens i.e. proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme.. This prospective study was carried out from July 1997 to February 1998. Sera were screened for ANCAs with indirect immunofluorescent test and tested with an enzyme immunoassay (ELISA) kit which provides a semi-quantitative assay for human IgG autoantibodies against 6 antigens: proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme.. A total of 75 patients were studied: 50 with IBD and 25 controls with functional bowel disease. Ten had Crohn's disease (CD) and 40 had ulcerative colitis (UC). There was no racial predilection among the Chinese, Malays or Indians. In CD, 1 was positive for cytoplasmic ANCA (cANCA) and 2 for perinuclear ANCA (pANCA). In UC, 4 were positive for pANCA, 15 for atypical perinuclear ANCA (apANCA) and 1 for cANCA. In the CD and UC population, the proportion positive for ANCA was 30% and 50%, respectively. There was no ANCA detected among the controls. Of those ANCA-positive IBD patients (n:23), only 1 demonstrated anti-myeloperoxidase antibodies. No antibodies were detected against the other 5 antigens tested.. This pilot Singapore study concludes that there is no significant ANCA association with proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Cathepsin G; Cathepsins; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Humans; Inflammatory Bowel Diseases; Lactoferrin; Male; Middle Aged; Muramidase; Myeloblastin; Pancreatic Elastase; Peroxidase; Pilot Projects; Prognosis; Prospective Studies; Reference Values; Sensitivity and Specificity; Serine Endopeptidases; Singapore

Inflammatory bowel disease (IBD) is an immune-mediated chronic inflammation of the intestine, which can present in the form of ulcerative colitis (UC) or as Crohn's disease (CD). Biomarkers are needed for reliable diagnosis and disease monitoring in IBD, especially in pediatric patients. Plasma samples from a pediatric IBD cohort were interrogated using an aptamer-based screen of 1322 proteins. The elevated biomarkers identified using the aptamer screen were further validated by ELISA using an independent cohort of 76 pediatric plasma samples, drawn from 30 CD, 30 UC, and 16 healthy controls. Of the 1322 proteins screened in plasma from IBD patients, 129 proteins were significantly elevated when compared with healthy controls. Of these 15 proteins had a fold change greater than 2 and 28 proteins had a fold change >1.5. Neutrophil and extracellular vesicle signatures were detected among the elevated plasma biomarkers. When seven of these proteins were validated by ELISA, resistin was the only protein that was significantly higher in both UC and CD (p < 0.01), with receiver operating characteristic area under the curve value of 0.82 and 0.77, respectively, and the only protein that exhibited high sensitivity and specificity for both CD and UC. The next most discriminatory plasma proteins were elastase and lactoferrin, particularly for UC, with receiver operating characteristic area under the curve values of 0.74 and 0.69, respectively. We have identified circulating resistin, elastase, and lactoferrin as potential plasma biomarkers of IBD in pediatric patients using two independent diagnostic platforms and two independent patient cohorts.

Topics: Biomarkers; Child; Colitis, Ulcerative; Crohn Disease; Humans; Inflammatory Bowel Diseases; Lactoferrin; Pancreatic Elastase; Proteomics; Resistin

Several studies indicate that the disruption of the intestinal epithelial barrier can lead to inflammatory bowel disease (IBD). Recent evidence has increasingly demonstrated that lactoferrin (LF) and osteopontin (OPN) can alleviate intestinal barrier injury. However, the potential synergistic effects of these two proteins and the mechanisms underlying their effects remain unclear. To address this question, we developed a lipopolysaccharide-induced intestinal barrier injury model in C57BL/6 N mice. Our findings demonstrated that the combination of LF and OPN at a 1:5 ratio exerts the strongest protective effect on the intestinal barrier, and it is more effective than LF or OPN alone. This protection is evidenced by the decrease in serum diamine oxidase (DAO) activity (1.66-fold decrease) and D-lactic content (1.51-fold decrease) and the reduced rate of FITC-labeled glucan transport across the jejunum (3.18-fold decrease). Moreover, the protein combination significantly promoted villi length (1.66-fold increase) and crypt depth (1.57-fold increase), improved tight junction protein structure and expression, and boosted the number of absorptive cells (4.34-fold increase) in the intestinal epithelium. Furthermore, the combination promoted crypt cell proliferation and differentiation via Notch signaling. In summary, our findings provide scientific evidence supporting the use of dietary intervention strategies for preventing IBD.

Topics: Animals; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Lactoferrin; Mice; Mice, Inbred C57BL; Osteopontin

The multifaceted effects of lactoferrin (LF) on the digestive and immune systems make it an attractive therapeutic option in inflammatory bowel diseases. In this study, we aimed to explore the anti-inflammatory effects of LF in colitis, particularly in relation to cellular senescence. We hypothesize that LF has the potential to modulate the senescence process. The effects of LF on senescence were tested in vitro using HCT116 and SW480 cell lines, and in vivo, the dextran sulfate sodium-induced mouse model of colitis. LF (500 mg/kg) alleviated symptoms of colitis in mice with a significant decrease in colon damage (P < .0001 vs. control) and microscopic (P < .05 vs. control) scores. Cellular senescence markers p16 and p21 were significantly upregulated in the mouse colon during inflammation (both P < .01 vs. control), and LF at 500 mg/kg decreased these markers (both P < .05 vs. dextran sulfate sodium-treated mice). In vitro, LF significantly affected the expression of p16 and p21 (P < .05-P < .0001 vs. control), senescence associated secretory phenotype (P < .01-P < .0001 vs. control), and telomere-specific proteins: telomeric repeat binding factor 1 and 2 (P < .05-P < .0001 vs. control) in a concentration-dependent manner. LF modulates the expression of cellular senescence markers and shows hallmarks of senolytic and pro-senescent activity, depending on dose. Further studies are needed to fully understand the anti-inflammatory effect of LF in the context of senescence and safe utilization in patients with inflammatory bowel diseases.

Topics: Animals; Anti-Inflammatory Agents; Cellular Senescence; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Humans; Inflammatory Bowel Diseases; Lactoferrin; Mice; Mice, Inbred C57BL

Fecal lactoferrin (FL) is a timely and accurate marker of inflammation in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to verify whether FL can predict primary nonresponse (PNR) to biologic agents during induction.. Retrospective outcome review in 27 patients (13 with CD and 14 with UC) tested for baseline FL and retested within a week after the first and second induction doses. Clinical/biochemical outcomes were evaluated at end of induction and at follow-up (3-24 months).. Compared to baseline, changes of the Harvey-Bradshaw (CD) and Partial Mayo Scoring (UC) indices at end of induction separated responders (18/27 or 67%) from nonresponders (9/17 or 33%). In all patients, the initial FL value at induction decreased compared to baseline, continuing to decrease after the following dose in clinical responders while bouncing back in the others. Models targeting the 2 consecutively decreased FL values or the second FL value compared to baseline or the second FL value compared to the first were able to accurately predict response at end of induction. Follow-up assessment confirmed clinical remission in initial responders (with FL values reduced on the average by 94 ± 10% compared to baseline).. In CD and UC patients during induction with biologic agents, early FL measurements accurately separate clinical responders from those experiencing PNR. The method described here offers several potential advantages over other strategies to assess and manage these patients.

Topics: Biological Factors; Biomarkers; Colitis, Ulcerative; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Remission Induction; Retrospective Studies

Lactoferrin and calprotectin are frequently ordered stool tests used to screen patients for inflammatory bowel disease versus functional bowel disease. Current guidelines recommend using either one to screen for inflammation in the GI tract; however, little information is available on how these 2 assays compare and their use in different clinical specialties.. We compared order patterns for lactoferrin and calprotectin using data from a large reference laboratory over a 10-y period (2009-2019). We also studied the concordance of lactoferrin and calprotectin in cases where both tests were ordered concurrently. Finally, we reviewed the records at a university hospital to determine which clinicians ordered each test and the indications associated with orders.. Orders for calprotectin are increasing relative to lactoferrin. The relative proportion of calprotectin orders have increased from 60% to nearly 90% over the past decade. Results for lactoferrin and calprotectin show concordance (90%). Calprotectin and lactoferrin are ordered by different clinical specialties for different indications. Calprotectin is most often ordered by gastroenterologists in the context of abdominal pain. Lactoferrin is most often ordered by primary care providers in the context of acute diarrhea.. Lactoferrin and calprotectin are not treated as equivalent tests by clinicians.

Topics: Biomarkers; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Occult Blood

Intestinal inflammation and increased intestinal permeability (both possibly fueled by dysbiosis) have been suggested to be implicated in the multifactorial pathogenesis of Parkinson's disease (PD). The objective of the current study was to investigate whether fecal markers of inflammation and impaired intestinal barrier function corroborate this pathogenic aspect of PD.. In a case-control study, we quantitatively analyzed established fecal markers of intestinal inflammation (calprotectin and lactoferrin) and fecal markers of intestinal permeability (alpha-1-antitrypsin and zonulin) in PD patients (n = 34) and controls (n = 28, group-matched for age) by enzyme-linked immunosorbent assay. The study design controlled for potential confounding factors.. Calprotectin, a fecal marker of intestinal inflammation, and two fecal markers of increased intestinal permeability (alpha-1-antitrypsin and zonulin) were significantly elevated in PD patients compared to age-matched controls. Lactoferrin, as a second fecal marker of intestinal inflammation, showed a non-significant trend towards elevated concentrations in PD patients. None of the four fecal markers correlated with disease severity, PD subtype, dopaminergic therapy, or presence of constipation.. Fecal markers reflecting intestinal inflammation and increased intestinal permeability have been primarily investigated in inflammatory bowel disease so far. Our data indicate that calprotectin, alpha-1-antitrypsin and zonulin could be useful non-invasive markers in PD as well. Even though these markers are not disease-specific, they corroborate the hypothesis of an intestinal inflammation as contributing factor in the pathogenesis of PD. Further investigations are needed to determine whether calprotectin, alpha-1-antitrypsin and zonulin can be used to define PD subgroups and to monitor the effect of interventions in PD.

Topics: Adult; Aged; alpha 1-Antitrypsin; Biomarkers; Case-Control Studies; Cholera Toxin; Feces; Female; Haptoglobins; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Parkinson Disease; Permeability; Protein Precursors; Severity of Illness Index

Clinical trials require valid outcome measures to assess the therapeutic benefit of investigational agents. Recently, regulatory authorities have mandated the use of patient-reported outcomes in combination with an objective measure of disease activity as primary outcome measures in inflammatory bowel disease trials. Endoscopy has commonly fulfilled the latter role; however, due to the costs and complexity of these assessments, interest has emerged in the use of noninvasive biomarkers. The role of C-reactive protein, fecal calprotectin, and fecal lactoferrin in clinical research is discussed.

Topics: Algorithms; Biomarkers; C-Reactive Protein; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Randomized Controlled Trials as Topic

Inflammatory bowel disease [IBD] is characterised by a disruption of immune homeostasis, which is tightly regulated to protect against harmful pathogens yet not react to commensal antigens. Animal studies indicate that regulatory T cells [Treg] modulate the immune response to prevent IBD development. Lactoferrin [LF] is an endogenous anti-inflammatory pleiotropic protein secreted at high concentrations in colostrum and at mucosal sites. However, the effect of LF on specific T lymphocyte populations has not been studied. Here, we identify a novel mechanism by which a recombinant human LF, VEN-120, regulates T cell populations in health and disease.. Two murine models of intestinal inflammation, the dextran sodium sulphate colitis model and the TNFΔARE/+ model of ileitis, were used to study the anti-inflammatory and T cell modulating ability of VEN-120. Flow cytometry was used to evaluate T cell populations within the lamina propria and mesenteric lymph nodes, and to evaluate the effect of VEN-120 on CD4+ T cells in vitro.. VEN-120 reduced inflammation in both models of IBD, accompanied by increased Tregs in the intestinal lamina propria. Treatment of CD4+ T cells in vitro resulted in an upregulation of Treg genes and skewing towards a Treg population. This in vitro T cell skewing translated to an increase of Treg homing to the intestinal lamina propria and associated lymph tissue in healthy mice.. These data provide a novel immunological mechanism by which VEN-120 modulates T cells to restrict inflammatory T cell-driven disease.

Topics: Animals; CD4-Positive T-Lymphocytes; Colitis; Flow Cytometry; Humans; Ileitis; Inflammatory Bowel Diseases; Lactoferrin; Mice; Mice, Inbred C57BL; Phenotype; Real-Time Polymerase Chain Reaction; Recombinant Proteins; T-Lymphocytes, Regulatory

Faecal calprotectin is considered to be a valid test for ruling out inflammatory bowel disease (IBD) in children with chronic gastrointestinal symptoms in specialist care. In contrast, faecal lactoferrin has higher specificity. The recent availability of both as point-of-care tests (POCTs) makes them attractive for use in primary care.. To evaluate the test characteristics of calprotectin and lactoferrin POCTs for diagnosing IBD in symptomatic children.. We defined two prospective cohorts of children with chronic gastrointestinal symptoms: (i) children presenting to primary care (primary care cohort); (ii) children referred for specialist care (referred cohort). Baseline POCT results were compared with the outcome of either endoscopic assessment or 12 months follow-up. Clinicians were blinded to the POCT results.. In the primary care cohort, none of the 114 children had IBD, and the calprotectin and lactoferrin POCTs had specificities of 0.95 (0.89-0.98) and 0.98 (0.93-0.99), respectively. In the referred cohort, 17 of the 90 children had IBD: the sensitivity of POCT calprotectin and POCT lactoferrin were both 0.94 (0.72-0.99); and the specificity was 0.93 (0.84-0.97) and 0.99 (0.92-1.00), respectively. The POCT calprotectin could reduce the referral rate by 76% and POCT lactoferrin by 81%, while missing one child with IBD (6%).. A diagnostic test strategy in primary care using a simple POCT calprotectin or lactoferrin has the potential to reduce the need for referral for further diagnostic work-up in specialist care, with a low risk of missing a child with IBD.

Topics: Adolescent; Biomarkers; Child; Cross-Sectional Studies; Feces; Female; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Pediatrics; Point-of-Care Systems; Primary Health Care; Prospective Studies; Referral and Consultation; Sensitivity and Specificity

Alterations in intestinal function, often characterized as a "leaky gut," have been attributed to children who are on the autism spectrum. Disaccharidase activity, intestinal inflammation, and permeability were analyzed in 61 children with autism and 50 nonautistic individuals with gastrointestinal symptoms.. All patients had duodenal biopsies assayed for lactase, sucrase, maltase, and palatinase activity. Intestinal permeability was evaluated by rhamnose/lactulose test and measured by high-performance liquid chromatography-mass spectrometry. Intestinal inflammation was evaluated by fecal calprotectin and lactoferrin levels using enzyme-linked immunosorbent assay and histology.. Some children with autism had mild levels of mucosal inflammation on intestinal biopsy. Disaccharidase activity was not different in autistic and nonautistic individuals. Fecal calprotectin and lactoferrin were similar in both groups. Differences between lactulose and rhamnose recovery and lactulose/rhamnose ratio in urine were not statistically different in patients with and without autism.. The present study supports the observation that children with autism who have symptoms of gastrointestinal disorders have objective findings similar to children without autism. Neither noninvasive testing nor endoscopic findings identify gastrointestinal pathology specific to autism, but may be of benefit in identifying children with autism who have atypical symptoms.

Topics: Adolescent; Autistic Disorder; Biopsy; Case-Control Studies; Child; Child Health Services; Duodenoscopy; Duodenum; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Lactoferrin; Leukocyte L1 Antigen Complex; Male

The optimization of procedure evaluating the severity of inflammatory bowel diseases (IBD) using non-invasive methods.. One hundred and nine children with IBD hospitalized in gastroenterology ward between 2009 and 2011 participated in the study. Activity of the disease was evaluated in each patient. Concentration of three inflammatory markers: dimeric form of tumor pyruvate kinase (M2-PK), calprotectin and lactoferrin was evaluated using immunoenzymatic tests.. Existence of a significant correlation between the faecal level of all tested markers and the stage of clinical activity of the disease was demonstrated in children with IBD, both in Crohn's disease (M2-PK p<0.01; calprotectin p=0.005; lactoferrin p<0.01) and in ulcerative colitis group (M2-PK p<0.01; calprotectin p=0.004; lactoferrin p<0.01). A significant difference in the level of markers was found between children with unclassified colitis and the group of patients with ulcerative colitis and Crohn's disease, but there was no difference between Crohn's disease and ulcerative colitis. The increase in the level of one marker correlated with increasing level of other markers (p<0.01). Faecal markers seem to correlate well with majority of indicators of inflammatory condition in blood.. Measuring M2-PK, lactoferrin and calprotectin levels in faeces seem to be a useful indicator of the level of disease activity in children with IBD.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Feces; Female; Humans; Inflammation; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Pyruvate Kinase

Topics: Blood Sedimentation; C-Reactive Protein; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte L1 Antigen Complex

Topics: Blood Sedimentation; C-Reactive Protein; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte L1 Antigen Complex

The aim of this study was to analyze the usefulness of fecal lactoferrin in the diagnosis and monitoring of inflammatory bowel disease (IBD) in children. The study included 52 children with IBD (24 with Crohn's disease and 28 with ulcerative colitis) aged between 0.92 and 18 years, and 41 IBD-free controls of similar age. Fecal concentration of lactoferrin was determined with a quantitative immunoenzymatic test. Fecal concentration of lactoferrin in children with IBD was significantly higher than in the controls. The cut-off value of fecal lactoferrin concentration optimally distinguishing between the children with IBD and the controls was identified as 13 μg/g. The sensitivity and specificity of this cut-off value equaled 80.7% and 92.7%, respectively, and its positive and negative prognostic values were 96.8% and 63.3%, respectively. Patients diagnosed with moderate Crohn's disease had significantly higher fecal concentrations of lactoferrin than children with the mild or inactive disease. Similarly, children with moderate ulcerative colitis showed significantly higher fecal concentrations of lactoferrin than individuals with the mild condition. No significant relationship was found between the fecal concentration of lactoferrin and the severity of endoscopic lesions. Patients with IBD and a positive result of fecal occult blood test were characterized by significantly higher concentrations of lactoferrin than the individuals with IBD and a negative result of this test. In conclusion, fecal concentration of lactoferrin seems to be a useful parameter for diagnosis and monitoring of IBD in children.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Colitis, Ulcerative; Crohn Disease; Feces; Female; Humans; Immunoenzyme Techniques; Infant; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Lactoferrin; Male; Predictive Value of Tests; Prognosis

Topics: Blood Sedimentation; C-Reactive Protein; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte L1 Antigen Complex

Topics: Blood Sedimentation; C-Reactive Protein; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte L1 Antigen Complex

Non-invasive markers able to identify patients with chronic diarrhea at risk of organic disease are missing. Aim of the study was to assess the diagnostic ability of intestinal permeability (IP) test and fecal lactoferrin (FL) in distinguishing functional from organic disease in patients with chronic diarrhea. We retrospectively enrolled patients referring to the gastroenterology outpatient clinic for chronic diarrhea. Among the 103 patients included, 40 % had an organic disease, with IP and FL levels significantly higher compared to those with a functional disorder (p < 0.0001). Sensitivity, specificity, positive and negative likelihood ratios, area under ROC curves of FL were superior to those of IP in discriminating functional and organic disease (FL: 87.8 and 93.6 %, 13.61 and 0.13, 0.9375; IP: 61.0 and 90.3 %, 6.3 and 0.43, 0.7691). When combining the two tests, the diagnostic ability of FL did not improve. In subgroup analysis, IP confirmed its ability to detect small bowel alterations, while FL could identify both small bowel and colonic alterations. In conclusion, FL is valid to detect inflammation in the gastrointestinal tract, while IP can effectively identify small bowel damage in chronic diarrhea patients. Together these tests could recognize both the presence of intestinal damage and its site.

Topics: Adult; Biomarkers; Chronic Disease; Diarrhea; Feces; Female; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Lactoferrin; Male; Middle Aged; Permeability; Retrospective Studies; Young Adult

Topics: Feces; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin

Distinguishing between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can be challenging.. To investigate the utility of faecal lactoferrin as a marker of inflammation in patients with IBD, IBS and controls.. Disease activity in IBD patients was assessed using the modified Harvey-Bradshaw Activity Index. Stool samples were analysed using an ELISA assay.. We recruited 137 patients with IBS, 126 with ulcerative colitis (UC) and 104 with Crohn's disease (CD), and 98 healthy volunteers. The median +/- IQ lactoferrin concentration (microg/g faecal weight) was 0 +/- 1.4 for IBS patients, 6.6 +/- 42 for UC patients, 4 +/- 12.7 for CD patients and 0.5 +/- 2 for healthy controls. Lactoferrin levels were significantly higher in IBD patients compared with IBS/healthy controls (P < 0.001). The median lactoferrin concentrations were significantly higher in active UC & CD patients compared with inactive patients (P < 0.001 and P = 0.002 respectively). The sensitivity, specificity, positive and negative predictive values of lactoferrin in distinguishing active IBD from IBS/healthy controls were 67% and 96%, 87% and 86.8% respectively.. Lactoferrin is useful to differentiate between IBD and IBS, and can be used as an adjunct to blood parameters to determine IBD patients who have ongoing inflammation.

Topics: Adult; Biomarkers; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Feces; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity; Statistics as Topic

Crohn's disease and ulcerative colitis have a feature in common (i.e., chronic inflammation). Their clinical management requires repeated assessments; endoscopy with histological examination remains the gold standard for detecting and quantifying intestinal inflammation. An ideal marker should be quick and easy to obtain noninvasively, and should be inexpensive and reproducible. Several laboratory tests have been studied but, to date, a disease marker is not yet available. A combination of signs and symptoms, laboratory findings and imaging techniques is consequently still needed for assessing disease activity and prognosis. In recent years, research has drawn attention to fecal markers owing to their specificity for intestinal inflammation, ease of sample collection, availability of commercial immunoassays and convenience. Biological markers have been used to assess inflammatory bowel disease patients for the purposes of their clinical management, monitoring disease activity, predicting relapses, assessing prognosis and monitoring response to treatment.

Topics: Biomarkers; Diagnosis, Differential; Feces; Humans; Inflammation; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Predictive Value of Tests; Prognosis

To evaluate whether fecal calprotectin (FC) and fecal lactoferrin (FL) can be used as noninvasive markers in children and young people (4-17 years) with active inflammatory bowel disease (IBD).. Stool samples were collected from 3 groups of children: those with active IBD, control individuals with other gastrointestinal (GI) diseases (GI control) and control individuals with no GI disease (non-GI control). The number of patients for the FC assay was as follows: IBD = 26, GI control = 30, non-GI control = 25. The number of patients for the FL assay was as follows: IBD = 24, GI control = 26, non-GI = 24. FC and FL were measured by use of enzyme-linked immunoassays.. The median concentrations of FC and FL in isolation, and their interaction, were significantly higher in the IBD group than in the GI and non-GI control groups (P < 0.001). Although the area under the curve, sensitivity, and specificity for FC, FL, and FC x FL interaction were significantly better than chance, FL consistently had the lowest area under the curve, and FC x FL consistently had the highest area under the curve.. FC and FL are both significantly elevated in children with IBD, and the interaction of these 2 biomarkers may produce a better initial diagnostic test compared with their use in isolation.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Feces; Gastrointestinal Diseases; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Logistic Models; Reference Values

The biomarkers are important in the Inflammatory Bowel Disease (IBD) to gain an objective measurement of disease activity and severity, as well as prognostic indicator and outcome of therapy. And they can be helpful to avoid invasive procedures. The ideal biomarker does not exist for IBD and it is likely that more than one biomarker will be needed. Biological markers potentially useful in IBD include acute-phase proteins, fecal markers, several antibodies and novel genetic determinants. The C-reactive protein (CRP) is the most studied and has been shown to be an objective marker of inflammation. CRP is a good marker of measuring disease activity in Crohn's disease (CD) and its levels can be used to guide therapy. The fecal markers (calprotectin and lactoferrin) may be helpful in differentiating patients with IBD from those with functional disorders and to predict clinical relapse. The panel of serologic markers (anti-Saccharomyces cerevisiae antibody, perinuclear anti-neutrophil cytoplasmic antibody, anti-OmpC and anti-I2 and antiglycan antibodies) for IBD can be used to stratify IBD patients into more homogeneous subgroups with respect to disease progression. Correlating serologic markers with genotypes and clinical phenotypes should enhance our understanding of the pathophysiology of IBD. The development of biomarkers in IBD will be very important in the future with the increasing utilization of novel methodological approaches like genomics and proteomics.

Topics: Acute-Phase Proteins; Algorithms; Antibodies; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; C-Reactive Protein; Diagnosis, Differential; Disease Progression; Evidence-Based Medicine; Feces; Humans; Immunoglobulin A; Immunologic Factors; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Practice Guidelines as Topic; Prognosis; Sensitivity and Specificity; Severity of Illness Index

Dextran sulfate sodium (DSS) induced intestinal inflammation is characterized by pronounced mucosal and epithelial cell damage. Bovine lactoferrin (bLf), a common dietary protein, influences inflammatory cytokines and intestinal lymphocyte (IL) apoptosis. The objectives of this study were to determine if 1) DSS induces IL necrotic or apoptotic death, 2) dietary bLf affects DSS induced IL death and 3) bLf alters cytokine profiles during DSS induced inflammation. Female C57BL/6 mice were randomized to 2% or 0% bLf diets for 12 d and within diets to 5% or 0% DSS in the drinking water for 4 d after which intestinal histology, IL number, IL apoptosis/necrosis, IL phenotypes, protein levels of pro-inflammatory cytokine (TNF-alpha) and transcription factor (NFkappaB), apoptotic (caspase 3, Bax) proteins, anti-inflammatory cytokine (IL-10) and anti-apoptotic (Bcl-2) protein in IL were evaluated. DSS treatment resulted in shortened intestinal length, decreased body weight and widespread mucosal damage as well as increased IL death as determined by a decreased percentage of viable (PI-/ANN-, P<0.005) and increased percentage of necrotic/late apoptotic (PI+/ ANN+, P<0.05) and necrotic (PI+/ANN-, P<0.05) IL. DSS exposure increased caspase 3 (P<0.05) and decreased Bcl-2 (P<0.01) protein levels in mouse IL. Dietary bLf did not influence these cell death outcome measures. However, bLf reduced protein levels of the pro-inflammatory transcription factor, NFkappaB, in IL (P<0.05) and was associated with a 34%, albeit non-significant, reduction in TNF-alpha relative to non-bLf fed mice. DSS treatment increased apoptosis and necrosis of mouse IL and elevated pro-apoptotic and reduced anti-apoptotic protein levels in these cells. Dietary bLf did not influence necrosis or apoptosis of IL but may provide limited protection in the intestine by affecting the pro-inflammatory transcription factor NFkappaB, and potentially, cytokine expression.

Topics: Animal Feed; Animals; Apoptosis; Body Weight; Caspase 3; Cattle; Dextran Sulfate; Eating; Female; Inflammatory Bowel Diseases; Interleukin-10; Lactoferrin; Lymphocytes; Mice; Mice, Inbred C57BL; NF-kappa B; Phenotype; Proto-Oncogene Proteins c-bcl-2; Tumor Necrosis Factor-alpha

Ruling out somatic bowel disease, such as inflammatory bowel disease (IBD), is an important goal in the management of abdominal complaints. Endoscopy is commonly used but is invasive and expensive. Mucosal inflammation in IBD can be detected through fecal biomarkers, though the present enzyme-linked immunoabsorbent assay (ELISA) tests require laboratory facilities. We validated the diagnostic performance of two new fecal rapid tests (FRTs) for the detection of calprotectin and lactoferrin and assessed their potential to differentiate IBD from irritable bowel syndrome (IBS).. The calprotectin and lactoferrin FRTs and ELISA tests were performed on the fecal samples of 114 patients referred for endoscopy, 80% of whom had IBS and 20% IBD, and validated against the endoscopic diagnosis.. The sensitivity and negative predictive value of the calprotectin FRT were both 100%, whereas they were 78% and 95%, respectively, for the lactoferrin FRT. The specificity and positive predictive value were slightly higher for the lactoferrin FRT. Both FRTs had similar diagnostic accuracy as the corresponding ELISA tests.. The calprotectin and lactoferrin rapid tests are as good as the ELISA tests in detecting colonic inflammation. Given their simple use, FRTs can support the non-invasive exclusion of IBD, notably in primary care.

Topics: Aged; Colon; Diagnosis, Differential; Endoscopy, Gastrointestinal; Enzyme-Linked Immunosorbent Assay; Feces; Female; Humans; Inflammation; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Reproducibility of Results; Sensitivity and Specificity; Time Factors

The aim of this study was to compare the performance of fecal lactoferrin (Lf), calprotectin (Cal), polymorphonuclear neutrophil elastase (PMN-e), as well as serum C-reactive protein (CRP) in patients with inflammatory bowel diseases (IBD) to address (a) whether these markers can differentiate IBD patients with endoscopically assessed inflammation from IBD patients without inflammation and from irritable bowel syndrome (IBS); (b) whether they correlate with endoscopic severity of inflammation; and (c) whether a combination of fecal markers with the respective disease-specific activity indices may increase the diagnostic accuracy with reference to the endoscopic severity of inflammation.. Fecal levels of Lf, Cal, and PMN-e and serum CRP were assessed in 139 patients undergoing diagnostic ileocolonoscopy (54 IBS patients, 42 ulcerative colitis [UC], 43 Crohn's disease [CD]). Disease activity was determined for CU with the colitis activity index (CAI) and for CD with the Crohn's disease activity index (CDAI). The performance of each marker with reference to endoscopic inflammatory activity was assessed by computing correlations, and sensitivity and specificity using published as well as adjusted cutoffs. A comprehensive activity index was computed by combining results from fecal markers, serum CRP, and a clinical activity index.. UC or CD patients with active inflammation demonstrated significantly higher levels of Lf, Cal, and PMN-e in feces as well as serum-CRP when compared to patients with inactive inflammation as well as patients with IBS (all P < 0.05). Using adjusted cutoffs enabled a marked improvement of all markers with an overall diagnostic accuracy in IBD of 80.0% for Lf, 80.0% for Cal, 74.1% for PMN-e, 64.0% for CRP, and 79.0% for the respective clinical disease scores. Cal showed the highest diagnostic accuracy in CD (81.4%), whereas Lf was superior to the other markers in UC (83.3%). The comprehensive activity index yielded a further improvement of sensitivity and specificity, with a diagnostic accuracy of 95.3% for UC patients.. The fecal markers Lf, Cal, and PMN-e are able to differentiate active IBD from inactive IBD as well as from IBS. None of these three stool markers is consistently superior in its ability to reflect endoscopic inflammation, but all three are superior to CRP in their diagnostic accuracy. A combination of the stool markers with the CRP and a disease-specific activity index in a categorical comprehensive activity index can increase the diagnostic accuracy with reference to the endoscopic inflammation in UC.

Topics: Adolescent; Adult; Aged; Biomarkers; C-Reactive Protein; Diagnosis, Differential; Disease Progression; Endoscopy, Gastrointestinal; Feces; Female; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte Elastase; Leukocyte L1 Antigen Complex; Male; Middle Aged; Prognosis; Sensitivity and Specificity; Severity of Illness Index

Symptoms of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can overlap. We aimed to determine the accuracy of fecal markers, C-reactive protein (CRP), blood leukocytes, and antibody panels for discriminating IBD from IBS and to define a "best test.". We prospectively included 64 patients with IBD (36 Crohn's disease [CD], 28 ulcerative colitis [UC]), 30 with IBS, and 42 healthy controls. Besides CRP and blood leukocytes, blinded fecal samples were measured for calprotectin (PhiCal Test, enzyme-linked immunosorbent assay [ELISA]), lactoferrin (IBD-SCAN, ELISA), Hexagon-OBTI (immunochromatographic test for detection of human hemoglobin), and LEUKO-TEST (lactoferrin latex-agglutination test). Blinded serum samples were measured for the antibodies ASCA (ELISA) and pANCA (immunofluorescence).. Overall accuracy of tests for discriminating IBD from IBS: IBD-SCAN 90%, PhiCal Test 89%, LEUKO-TEST 78%, Hexagon-OBTI 74%, CRP 73%, blood leukocytes 63%, CD antibodies (ASCA+/pANCA- or ASCA+/pANCA+) 55%, UC antibodies (pANCA+/ASCA-) 49%. ASCA and pANCA had an accuracy of 78% for detecting CD and 75% for detecting UC, respectively. The overall accuracy of IBD-SCAN and PhiCal Test combined with ASCA/pANCA for discriminating IBD from IBS was 92% and 91%, respectively.. The PhiCal Test and IBD-SCAN are highly accurate for discriminating IBD from IBS. There is only marginal additional diagnostic accuracy when the PhiCal Test and IBD-SCAN are combined with ASCA and pANCA. ASCA and pANCA have a high specificity for IBD.

Topics: Adult; Aged; Antibodies, Fungal; C-Reactive Protein; Carrier Proteins; Diagnosis, Differential; Feces; Female; Hemoglobins; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte Count; Leukocyte L1 Antigen Complex; Male; Middle Aged; Prospective Studies; Sensitivity and Specificity

Calprotectin and lactoferrin are specific neutrophil-derived proteins, which can be measured in the feces because they are released by cells in inflammatory conditions. We evaluated the efficacy of calprotectin and lactoferrin in detecting organic disease as assessed by colonoscopy.. The study comprised 144 patients undergoing colonoscopy for lower gastrointestinal symptoms (abdominal pain, altered bowel habits, and bloody stools) (67), or inflammatory bowel disease activity, or surveillance for dysplasia (77). A single stool sample was assayed for calprotectin and lactoferrin. The proportion of patients correctly diagnosed with each test and the relationship with endoscopic and histological findings were measured.. Fecal excretion of calprotectin significantly correlated with the finding of colonic inflammation at endoscopy, both in ulcerative colitis and in Crohn's disease (p<0,001 and p<0,008, respectively), while lactoferrin excretion significantly correlated with histological inflammation (p=0.001 and p=0.009 respectively). Recommended cut-off values need to be adjusted in the inflammatory bowel disease group. Overall sensitivity, specificity, positive predictive value, and diagnostic efficacy were 78, 83, 86, and 80% for calprotectin and 80, 85, 87, and 81% for lactoferrin, respectively.. Fecal calprotectin and lactoferrin appear to be equally recommendable as inflammatory disease markers in patients with lower gastrointestinal symptoms. Both tests are needed to accurately discriminate activity in inflammatory bowel disease patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Colitis, Ulcerative; Colonoscopy; Crohn Disease; Feces; Female; Gastroenteritis; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity

Fecal lactoferrin (FLA) is a neutrophil-derived surrogate marker of intestinal inflammation that is elevated in patients with inflammatory bowel disease. However, the correlation between FLA levels and serological markers of disease activity has not been previously reported, to our knowledge. In the present study we evaluated the ability of FLA levels to reflect disease activity in pediatric patients with inflammatory bowel disease. We further assessed the relationship between FLA levels and customary laboratory and clinical measures of inflammation.. Fecal specimens were collected from 148 consecutive pediatric patients (79 with Crohn disease, 62 with ulcerative colitis, and 7 with irritable bowel syndrome) and 22 healthy control individuals. Lactoferrin was measured by enzyme-linked immunosorbent assay (IBD-SCAN, TECHLAB, Inc). Disease activity was assessed at the time of sample provision by laboratory measures (including erythrocyte sedimentation rate [ESR] and albumin) and previously validated disease activity indices (Pediatric Crohn Disease Activity Index, Kozarek, Harvey Bradshaw Activity Index).. Lactoferrin levels were significantly higher in patients with ulcerative colitis (1880 +/- 565 microg/mL) (mean +/- SE) or Crohn disease (1701 +/- 382 microg/mL) than in healthy control individuals under 21 years of age (1.17 +/- 0.47 microg/mL, P < 0.001). Lactoferrin levels correlated significantly with ESR, hematocrit, albumin, and platelet count (P < 0.001). Receiver operating characteristic curve analysis revealed that FLA levels were comparable to ESR in detecting patients with clinically active disease (P < 0.001). Patients who experienced a clinical flare within 2 months of specimen collection displayed higher lactoferrin levels (845 +/- 452 microg/mL) than did those who remained in clinical remission (190 +/- 90 microg/mL, P = 0.003).. Data presented here demonstrate that FLA is a sensitive and specific biochemical marker of inflammation for use in the diagnosis and interval assessment of pediatric patients with IBD, and its level correlates well with both clinical disease activity indices and ESR. Elevated levels of FLA may also identify patients at greater risk for the development of subsequent clinical flares.

Topics: Adolescent; Adult; Biomarkers; Child; Child, Preschool; Feces; Female; Humans; Inflammatory Bowel Diseases; Lactoferrin; Male; Sensitivity and Specificity

Poorly absorbed short-chain carbohydrates (FODMAPs) in the diet should, by virtue of their osmotic effects, increase fecal output following colectomy and ileal pouch formation or ileorectal anastomosis (IRA). The aim was to perform a proof-of-concept evaluation of this hypothesis.. Fifteen patients (13 pouch, 2 IRA) had dietary and symptomatic evaluation before and during a low FODMAP diet. Carbohydrate malabsorption was evaluated by breath tests. Pouchitis was assessed clinically/endoscopically or by fecal lactoferrin.. Of 8 patients with a breath hydrogen response to lactulose, 7 had fructose malabsorption, 3 with lactose malabsorption, and 1 had lactose malabsorption alone. Five of 7 studied retrospectively improved stool frequency (from median 8 to 4 per day; P = 0.02), this being sustained over 0.5-3 years of follow-up. Five of 8 patients completed a prospective arm of the study. One patient had sustained improvement in stool frequency and 1 had reduced wind production. Overall, none of 8 patients who had pouchitis improved. In contrast, median daily stool frequency fell from 8 to 4 (P = 0.001) in the 7 without pouchitis. The degree of change in FODMAP intake also predicted response. There was a tendency for pouchitis to be associated with low baseline FODMAP intake.. There is a high prevalence of carbohydrate malabsorption in these patients. Reduction of the intake of FODMAPs may be efficacious in reducing stool frequency in patients without pouchitis, depending on dietary adherence and baseline diet.

Topics: Adult; Aged; Breath Tests; Diet Therapy; Endoscopy, Gastrointestinal; Feces; Female; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Lactoferrin; Malabsorption Syndromes; Male; Middle Aged; Oligosaccharides; Pilot Projects; Pouchitis

Lactoferrin as a glucoprotein that can reflect the activity of neutrophil leukocytes is a specific and sensitive indicator in the evaluation of intestinal inflammation. The aim of this study was to evaluate the relationship between fecal lactoferrin and intestinal inflammation by quantitative analysis and the effect of fecal lactoferrin in measuring the activity of inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD).. A total of 177 fresh stool samples were collected from 42 active UC, 17 inactive UC, 13 active CD, 5 inactive CD, 41 infectious bowel disease, 25 irritable bowel syndrome (IBS) and 34 healthy volunteers. IBD-SCAN was used quantitatively to measure the level of fecal lactoferrin. A modified Harvey-Bradshaw Active Index was used to evaluate the activity of IBD.. Fecal lactoferrin was 3.15+/-1.60 microg/g in healthy volunteers, 2.54+/-1.49 microg/g in IBS, 83.3+/-29.9 microg/g in infectious bowel disease, 1126.29+/-431.21 microg/g in active UC, 1035.25+/-456.59 microg/g in active CD, 96.58+/-82.46 microg/g in inactive UC and 133.52+/-88.89 microg/g in inactive CD. Fecal lactoferrin was significantly higher in active IBD than in inactive IBD, IBS and infectious bowel disease. The sensitivity and specificity of fecal lactoferrin were 92% and 88%, respectively, for UC, and 92% and 80%, respectively, for CD.. Fecal lactoferrin is a sensitive and specific marker in measuring the activity of IBD. It provides us with a valid method in discriminating between inflammatory and non-inflammatory bowel disease. In addition, an elevated fecal lactoferrin level can lead us to exclude IBS in clinical practice.

Topics: Adolescent; Adult; Aged; Biomarkers; Enzyme-Linked Immunosorbent Assay; Feces; Female; Humans; Inflammatory Bowel Diseases; Lactoferrin; Linear Models; Male; Middle Aged; Sensitivity and Specificity; Statistics, Nonparametric

The aim of this prospective study was to compare five different leukocyte proteins in feces of patients with chronic inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and healthy persons who underwent prophylactic colonoscopy.. The leukocyte proteins calprotectin, lactoferrin, lysozyme, myeloperoxidase, and PMN-elastase were determined with immunoassays in fecal samples of three consecutive feces (e.g. three days) in 40 healthy persons, 39 patients with chronic IBD (of these 21 with Crohn's disease and 18 with ulcerative colitis), and 40 patients with IBS.. ROC curves calculated for healthy persons and patients with IBD yielded the following areas under the curves (AUCs): PMN-elastase 0.916, calprotectin 0.872, myeloperoxidase 0.750, lysozyme 0.726, and lactoferrin 0.693. The AUCs of PMN-elastase and calprotectin were not significantly different (p = 0.327), whereas PMN-elastase or calprotectin vs. the other proteins were significantly different (p < 0.001). PMN-elastase and calprotectin correlated with the endoscopically classified severity of inflammation. All fecal leukocyte markers in IBS were found in the range of the healthy persons. Data on storage stability of leukocyte proteins in fecal supernatants are given.. Fecal PMN-elastase and calprotectin support the differentiation of chronic IBD from IBS and correlate with the severity of inflammation.

Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Feces; Female; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Leukocyte Elastase; Leukocyte L1 Antigen Complex; Leukocytes; Male; Middle Aged; Muramidase; Peroxidase; Prognosis; Prospective Studies; ROC Curve

Increased stool frequency, urgency, and abdominal pain in patients with ileal pouch-anal anastomosis (IPAA) may be due to inflammatory conditions, including pouchitis, cuffitis, or Crohn's disease or noninflammatory conditions such as irritable pouch syndrome. Distinction among these entities requires pouch endoscopy and biopsy. Noninvasive means of diagnosis are preferable.. Sixty consecutive subjects with IPAA for inflammatory bowel disease had measurements of fecal lactoferrin and alpha1-antitrypsin and underwent pouch endoscopy with biopsy, with calculation of the pouchitis disease activity index in a prospective cross-sectional study.. Symptomatic patients with an inflammatory condition had significantly higher fecal lactoferrin concentrations (median, 176.0 microg/mL, interquartile range [IQR] 79.0-450.8) compared with those with a noninflammatory condition (median, 4.8 microg/mL; IQR, 1.2-11.0) or those who were asymptomatic (median, 7.8 microg/mL; IQR, 1.4-12.9), P < 0.001. At a cutoff level of 7 microg/mL, fecal lactoferrin could distinguish patients with irritable pouch syndrome from those with pouchitis, cuffitis, or Crohn's disease with a sensitivity of 100% and specificity of 85%. Fecal alpha1-antitrypsin was not able to distinguish symptomatic patients with and without an inflammatory condition.. Fecal lactoferrin can serve as a sensitive and noninvasive initial screening test in an algorithm for evaluation of symptomatic patients with IPAA. If fecal lactoferrin levels are low (<7 microg/mL), IPS can be diagnosed. If fecal lactoferrin levels are high, pouch endoscopy with biopsy is warranted to distinguish among different causes of inflammation. Longitudinal studies are needed to define better the role of this test in the management of patients with IPAA.

Topics: Adult; Algorithms; alpha 1-Antitrypsin; Anal Canal; Anastomosis, Surgical; Colonic Pouches; Crohn Disease; Cross-Sectional Studies; Diagnosis, Differential; Feces; Female; Humans; Inflammatory Bowel Diseases; Lactoferrin; Male; Middle Aged; Pouchitis; Prospective Studies; Sensitivity and Specificity

Lactoferrin is a glycoprotein expressed by activated neutrophils. The aim of this study was to determine the sensitivity and specificity of fecal lactoferrin concentrations for inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) versus healthy controls.. Fresh stool samples were collected from outpatients with ulcerative colitis (UC), Crohn's disease (CD), or IBS. Clinical disease activity for IBD was assessed using a modified Harvey-Bradshaw Activity Index. Fecal lactoferrin concentrations were determined using a polyclonal antibody-based enzyme linked immunoassay. Mean fecal lactoferrin concentrations for each group and sensitivity and specificity of the assay were determined.. One hundred-four CD patients, 80 UC patients, 31 IBS patients, and 56 healthy controls were recruited. The mean +/- SE fecal lactoferrin concentration (microg/g fecal weight) was 440 +/- 128 for CD patients, 1125 +/- 498 for UC patients, 1.27 +/- 0.29 for IBS patients, and 1.45 +/- 0.4 for healthy controls. Fecal lactoferrin was 90% specific for identifying inflammation in patients with active IBD. Elevated fecal lactoferrin was 100% specific in ruling out IBS.. Fecal lactoferrin is sensitive and specific for detecting inflammation in chronic IBD. This noninvasive test may prove useful in screening for inflammation in patients presenting with abdominal pain and diarrhea.

Topics: Adolescent; Adult; Aged; Biomarkers; Child; Colonic Diseases, Functional; Enzyme-Linked Immunosorbent Assay; Feces; Female; Humans; Inflammatory Bowel Diseases; Lactoferrin; Male; Middle Aged; Sensitivity and Specificity; Severity of Illness Index

Routine stool culture is used to evaluate patients with diarrheal illness. However, the results are often delayed, and the tests are very expensive. Therefore a rapid, simple method for screening would be a helpful adjunct in a diagnostic algorithm. Fecal leukocytes are found in diarrhea patients with diffuse colonic inflammation but missing in non-inflammatory cases, and are most commonly identified in infectious diarrheas of bacterial origin. It supports the use of immediate empiric therapy in very young, elderly and immunocompromised individuals. When negative, it may eliminate the need for stool culture in some cases of diarrhea. Recently, a new latex bead assay has been developed for the detection of lactoferrin, an iron binding glycoprotein found in polymorphonuclear leukocytes.. Evaluate the value of fecal leukocytes and lactoferrin in the workup of patients with diarrhea.. Fecal samples of 50 consecutive adult patients with acute or chronic diarrhea were tested for fecal leukocytes and lactoferrin. The results were compared with findings from fecal cultures, tests for parasite, Clostridium difficile A toxin latex test, data of the gastrointestinal examination and clinical evaluation. The authors defined two groups of the cases: the inflammatory and non-inflammatory diarrheas.. The sensitivity, specificity, positive and negative predictive value of microscopic leukocyte count and the lactoferrin test were 42 and 63%, 87 and 87%, 67 and 75%, 71 and 79% respectively.. In agreement with the literature the results of the present study indicate that fecal lactoferrin appears more sensitive than fecal leukocyte smear, and accurately rules out inflammatory diarrhea.

Topics: Adult; Aged; Algorithms; Diagnosis, Differential; Diarrhea; Enteritis; Feces; Female; Humans; Inflammatory Bowel Diseases; Intestinal Diseases, Parasitic; Lactoferrin; Leukocyte Count; Leukocytes; Male; Mass Screening; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity

Alteration of mucosal and systemic immune responses may play an important role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to evaluate natural immune responses (i.e., phagocytosis, killing, and antibacterial activity), serum autoantibodies (antineutrophil cytoplasmic antibodies [ANCA] and anti-lactoferrin [LF] antibodies), and plasma endotoxins in patients affected by ulcerative colitis (UC) and Crohn's disease (CD).. Blood samples were obtained from 71 patients with UC, 32 patients with CD, and 32 control subjects. Disease activity was scored using Truelove's criteria in patients with UC and the Crohn's Disease Activity Index (CDAI) in patients with CD. Candida albicans served as a target for evaluation of phagocytosis and killing exerted by polymorphonuclear cells (PMN) and monocytes (MO), whereas Salmonella typhi was used for assessing lymphocyte-mediated antibacterial activity. ANCA were detected by indirect immunofluorescence, whereas anti-LF antibodies were assayed by means of enzyme-linked immunosorbent assay. Plasma endotoxins were measured by Limulus amoebocyte lysate assay.. Phagocytosis and killing exerted by PMN and MO, as well as lymphocyte-mediated antibacterial activity, were significantly reduced (p < 0.0001) in patients affected by UC and CD in comparison with controls, irrespective of either disease activity or treatment. Plasma endotoxins were detected in 12/71 (17%) patients with UC, and in 10/32 (31%) patients with CD. ANCA were present in 42/71 (59%) patients with UC and in 3/32 (9%) patients with CD, whereas anti-LF antibodies were detected in 31 (44%) UC patients and in six (19%) CD patients. No significant differences in phagocytosis and killing exerted by PMN were found between ANCA-positive and ANCA-negative UC patients.. Our data demonstrate an impairment of natural immunity exerted by peripheral blood phagocytes and lymphocytes in patients with UC and CD. ANCA and anti-LF antibodies were present mainly in UC patients but their presence did not affect PMN-mediated phagocytosis and killing. Finally, plasma endotoxins may contribute to the chronic inflammatory status, likely by inducing release of proinflammatory mediators.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Blood Bactericidal Activity; Cell Death; Colitis, Ulcerative; Crohn Disease; Endotoxins; Female; Humans; Inflammatory Bowel Diseases; Lactoferrin; Lymphocytes; Macrophages; Male; Middle Aged; Neutrophils; Phagocytosis

Our aim was to investigate the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in Japanese patients with ulcerative colitis (UC) and Crohn's disease (CD), and the putative antigens recognized by perinuclear staining pattern ANCA (p-ANCA)-positive sera.. Sera from UC (n = 52) and CD (n = 43) patients, and from healthy controls (n = 74) were studied. The indirect immunofluorescence (IIF) method was used for the detection of ANCA and its binding pattern. p-ANCA-positive sera were studied further for putative antigens. ELISAs using lactoferrin (Lf), myeloperoxidase (MPO), and cathepsin G (Cat G) as antigens were performed.. ANCA was positive in 40 of the 52 (76.9%) UC (p-ANCA in 33) and in 32 of the 43 (74.4%) CD (p-ANCA in 31) patients. UC and CD patients showed significantly higher titers of p-ANCA than controls; however, no significant difference was observed between UC and CD. In UC, 23, 17, and nine of the 33 patients with p-ANCA-positive sera showed reactivity with Lf, MPO, and Cat-G, respectively. In CD, 21, 20, and 11 of the 31 patients with p-ANCA-positive sera showed reactivity with Lf, MPO, and Cat-G, respectively. Fourteen of the UC and six of the CD patients showed reactivity with two different antigens, and seven of the UC and 11 of the CD patients showed reactivity with all three antigens. The presence of anti-Lf and anti-MPO antibodies was further confirmed by Western blotting.. ANCA is useful in distinguishing patients with IBD from normal subjects but is not sufficient for the differential diagnosis of CD and UC. p-ANCA reactivity might be derived from the recognition of heterogeneous neutrophil-associated antigens.

Topics: Adult; Animals; Antibodies, Antineutrophil Cytoplasmic; Antigen-Antibody Reactions; Antigens; Binding, Competitive; Biomarkers; Cathepsin G; Cathepsins; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin G; Inflammatory Bowel Diseases; Japan; Lactoferrin; Milk; Peroxidase; Serine Endopeptidases; Serum Albumin, Bovine

Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against cytoplasmic constituents of neutrophil granulocytes. Antibodies with specificity for proteinase 3 and myeloperoxidase are seromarkers for systemic vasculitides. ANCA with specificity for lactoferrin were described in patients with several idiopathic inflammatory diseases, such as the inflammatory bowel diseases and rheumatoid arthritis. However, the clinical significance of anti-lactoferrin autoantibodies is still unclear. In this study, we determined the clinical significance of anti-lactoferrin autoantibodies in sera from large groups of patients with ulcerative colitis (UC), Crohn's disease (CD), and primary sclerosing cholangitis (PSC). Antibodies to human lactoferrin were detected by ELISA and by immunoblotting, using an extract of sonicated neutrophils as antigen source. Autoantibodies to lactoferrin were found in 29% of patients with UC, 13% of patients with CD, and 22% of patients with PSC. In inflammatory bowel diseases, the presence of anti-lactoferrin antibodies was not related to treatment, disease activity, duration of disease, or disease extent. In PSC, the presence of autoantibodies to lactoferrin did not correlate with duration of disease or the presence of cirrhosis. However, patients with PSC and coexistent UC had significantly more frequently antibodies to lactoferrin than PSC patients without IBD. In conclusion, autoantibodies to lactoferrin are a common feature of inflammatory bowel diseases and PSC. However, the clinical significance of those autoantibodies is limited as they lack sensitivity and specificity for those disorders. Future research should address the pathophysiological role of anti-lactoferrin ANCA and the influence of anti-lactoferrin ANCA binding on the functional properties of the lactoferrin molecule.

Topics: Autoantibodies; Autoantigens; Cholangitis, Sclerosing; Enzyme-Linked Immunosorbent Assay; Humans; Immunoblotting; Inflammatory Bowel Diseases; Lactoferrin

1. Faecal excretion of the leucocyte primary granule component, myeloperoxidase, and of the secondary granule component, lactoferrin, were compared in inflammatory bowel disease and infective diarrhoea. 2. Faecal lactoferrin correlated with faecal myeloperoxidase in both inflammatory bowel disease (P = 0.0018; n = 32) and infective diarrhoea (P = 0.00013; n = 37), but inflammatory bowel disease was associated with a much higher faecal excretion of lactoferrin but lower excretion of myeloperoxidase than infective diarrhoea. As a consequence, the median ratio of lactoferrin/myeloperoxidase excretion (both expressed as ng/mg of protein) for inflammatory bowel disease was 7.5 (range 3.5-21.3) with similar values for ulcerative colitis (n = 18) and Crohn's disease (n = 14) compared with only 0.9 (range 0.4-2.3; P < 0.0001) for infective diarrhoea. In inflammatory bowel disease faecal lactoferrin and myeloperoxidase excretion remained increased even in clinical remission. 3. In subsequent immunohistochemical studies to assess the possible explanation for these findings, lactoferrin and myeloperoxidase were demonstrated within crypt abscesses and surface mucus, both in inflammatory bowel and in infective diarrhoea mucosal samples. There was a slight increase in the number of lactoferrin-containing cells in the mucosal samples from ulcerative colitis and in the submucosa of samples from Crohn's disease compared with infective diarrhoea, but these changes were not sufficient to account for the marked increase in faecal lactoferrin excretion in inflammatory bowel disease. 4. In all mucosal samples, including those from normal mucosa, lactoferrin was also shown to be contained within mast cells. 5. These results could best be explained by a different mechanism for leucocyte activation in inflammatory bowel disease compared with infective diarrhoea, and are compatible with selective secretion of secondary granule components, which include lactoferrin but not myeloperoxidase, as a result of leucocyte activation by N-formylated bacterial peptides in inflammatory bowel disease.

Topics: Bacterial Infections; Colitis, Ulcerative; Crohn Disease; Diarrhea; Feces; Humans; Immunohistochemistry; Inflammatory Bowel Diseases; Intestinal Mucosa; Lactoferrin; Lymphocyte Activation; Mast Cells; Peroxidase; Saliva

To characterize the antigen specificity of circulating anti-neutrophil cytoplasmic antibodies (ANCAs) in inflammatory bowel disease (IBD).. Analysis of the prevalence of circulating ANCAs in patients with ulcerative colitis and Crohn's disease, by both non-specific methods (immunofluorescence against fixed neutrophil leukocytes) and specific antigen techniques (against purified neutrophil leukocyte constituents).. Indirect immunofluorescence against fixed polymorphonuclear leukocytes, and solid-phase enzyme-linked immunosorbent assay (ELISA) against neutrophil constituents (alpha-granules, elastase, myeloperoxidase, cathepsin g, lysozyme and lactoferrin).. Although results using immunofluorescence were typical of other studies (ulcerative colitis positive in 41%, Crohn's disease in 10%), ELISA studies showed antibody activity against neutrophil components in 69% of patients with ulcerative colitis and 39% of those with Crohn's disease. Antibodies in ulcerative colitis were commonly directed (in descending order) against lysozyme, cathepsin G, elastase, and lactoferrin, and in Crohn's disease against lysozyme.. Correlation of indirect immunofluorescence data and ELISA results indicated that even this large panel of specific antigens fails to identify all the ANCA targets in IBD. The lack of correlation between the findings of ANCAs, either in general or versus a specific target, and disease extent or activity in ulcerative colitis supports the suggestion that ANCAs are unlikely to be of primary importance in pathogenesis.

Topics: Adult; Aged; Antibodies; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Cathepsin G; Cathepsins; Cholangitis, Sclerosing; Colitis, Ulcerative; Crohn Disease; Cytoplasmic Granules; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin G; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte Elastase; Male; Middle Aged; Muramidase; Neutrophils; Pancreatic Elastase; Peroxidase; Serine Endopeptidases; Vasculitis

Anti-neutrophil cytoplasmic antibodies (ANCA) were observed in 31 out of 68 sera (45%) from Ulcerative Colitis (UC) patients and in 13 out of 38 Crohn's Disease (CD) sera (34%). The presence of ANCA was not related to disease activity, nor to the localization of the disease manifestations. By Western Blotting ANCA showed reactivity with either lactoferrin, polypeptides occurring as a doublet of 66/67 kD MW, or polypeptides occurring as a doublet of 63/54 kD MW.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Autoantibodies; Autoantigens; Blotting, Western; Colitis, Ulcerative; Crohn Disease; Humans; Immunoglobulin G; Inflammatory Bowel Diseases; Lactoferrin

The nucleophilic properties of human lactoferrin (Lf) were demonstrated by immunofluorescence microscopy using cryostat rat tissue sections, and the nuclear/perinuclear distribution of Lf in ethanol-fixed human neutrophils was visualized with rabbit anti-human Lf, producing a P-ANCA/GS-ANA staining pattern. Prevention of complement activation by Lf was confirmed in a haemolytic assay. Antibodies (IgG) against human Lf were studied by ELISA in sera from patients with Crohn's disease, ulcerative colitis, primary sclerosing cholangitis, rheumatoid arthritis, systemic lupus erythematous and primary Sjögren's syndrome. Anti-Lf antibodies were found in high frequency in ulcerative colitis and primary sclerosing cholangitis, but only occasionally in the other conditions.

Topics: Animals; Colitis, Ulcerative; Crohn Disease; Fluorescent Antibody Technique; Humans; Inflammatory Bowel Diseases; Lactoferrin; Luminescent Measurements; Milk, Human; Neutrophils; Rats