lactoferrin and Crohn-Disease

The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins.. A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence.. The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data.. None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.

Topics: Biomarkers; Crohn Disease; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Severity of Illness Index

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

Ileocolonoscopy is the gold standard for the diagnosis and assessment of postoperative recurrence in Crohn's disease (CD). Nevertheless, endoscopy is time-consuming and invasive. A minimally invasive and simple screening test would improve patient adherence to examination and provide greater clinical benefit. A number of fecal biomarkers have been evaluated for their utility for the diagnosis and monitoring of inflammatory bowel disease as alternative tests to endoscopy. Area covered: In this review, we focused on the utility of fecal biomarkers in the management of postoperative CD. Our major endeavor was to present an evidence-based assessment of the results of clinical trials on the available data. A literature search was conducted using the Medline. Expert commentary: Calprotectin and lactoferrin, both neutrophil-derived proteins, are the two most frequently used fecal biomarkers in clinical trials and practice. Several studies evaluated the role of these fecal biomarkers in patients with postoperative CD. These studies suggest that fecal calprotectin, and to a lesser degree lactoferrin, are useful in assessing endoscopic severity and in predicting future clinical recurrence after resection for CD. However, large scale, well-designed studies are necessary to rigorously evaluate the role of fecal biomarkers in postoperative CD.

Topics: Biomarkers; Colonoscopy; Crohn Disease; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Mass Screening; Recurrence

Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD). Therefore, monitoring of patients with intent to suppress subclinical inflammation has emerged as a treatment concept. As endoscopic monitoring is invasive and resource intensive, identification of valid markers of disease activity is a priority. The objective was to evaluate the diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and stool lactoferrin (SL) for assessment of endoscopically defined disease activity in IBD.. Databases were searched from inception to November 6, 2014 for relevant cohort and case-control studies that evaluated the diagnostic accuracy of CRP, FC, or SL and used endoscopy as a gold standard in patients with symptoms consistent with active IBD. Sensitivities and specificities were pooled to generate operating property estimates for each test using a bivariate diagnostic meta-analysis.. Nineteen studies (n=2499 patients) were eligible. The pooled sensitivity and specificity estimates for CRP, FC, and SL were 0.49 (95% confidence interval (CI) 0.34-0.64) and 0.92 (95% CI 0.72-0.96), 0.88 (95% CI 0.84-0.90) and 0.73 (95% CI 0.66-0.79), and 0.82 (95% CI 0.73-0.88) and 0.79 (95% CI 0.62-0.89), respectively. FC was more sensitive than CRP in both diseases and was more sensitive in ulcerative colitis than Crohn's disease.. Although CRP, FC, and SL are useful biomarkers, their value in managing individual patients must be considered in specific clinical contexts.

Topics: Biomarkers; C-Reactive Protein; Colitis, Ulcerative; Crohn Disease; Endoscopy, Gastrointestinal; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Sensitivity and Specificity

Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing characterization of the mechanistic process through which milk components promote development and immunity has revealed numerous milk-derived compounds with potential applications as clinical therapies in infectious and inflammatory disease, cancer, and other conditions. Lactoferrin is an effective antimicrobial and antiviral agent in high-risk patient populations and a potentially potent adjuvant to chemotherapy in lung cancer. Enteric nutrition formulas supplemented with transforming growth factor β, a milk cytokine, have been shown to promote remission in pediatric Crohn's disease. A number of milk glycans, including human milk oligosaccharides, show promise in preclinical studies as antimicrobial and anti-inflammatory agents. While active preclinical investigations of human milk may soon result in large-scale production of human milk molecules, bovine milk components in many instances represent a practical source of bioactive milk compounds for use in clinical trials. This review summarizes current efforts to translate the compounds derived from human and bovine milk into effective clinical therapies. These efforts suggest a common pathway for the translation of milk-derived compounds into clinical applications.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Caseins; Cattle; Cell Line, Tumor; Crohn Disease; Humans; Lactalbumin; Lactoferrin; Milk; Milk, Human; Oligosaccharides; Randomized Controlled Trials as Topic; Transforming Growth Factor beta

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

Diagnosis and monitoring of inflammatory bowel diseases rely on clinical, endoscopic, and radiologic parameters. Inflammatory biomarkers have been investigated as a surrogate marker for endoscopic diagnosis of inflammatory activity. Fecal inflammatory biomarkers such as calprotectin and lactoferrin are direct products of bowel inflammation and provide an accurate and noninvasive diagnostic and monitoring modality for Crohn's disease and ulcerative colitis. This report contains an overview of the currently existing literature pertaining to clinical implications of fecal biomarkers for diagnosis, monitoring, and prediction of outcomes of inflammatory bowel disease.

Topics: Biomarkers; Colitis, Ulcerative; Crohn Disease; Disease Progression; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Matrix Metalloproteinases; Predictive Value of Tests; Pyruvate Kinase; Recurrence; S100 Proteins; S100A12 Protein; Severity of Illness Index; Treatment Outcome

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

Recurrence of Crohn's disease following surgical resection is common, but the optimal strategy to assess, prevent, and treat postoperative recurrence remains unclear. Recent developments in the prevention and management of postoperative recurrence have provided additional information.. Predictors of Crohn's disease recurrence after surgery include cigarette smoking, disease behavior, number of prior resections, family history, anastomotic type, and time to first surgery. Only penetrating disease behavior and continued cigarette smoking after surgery remain clear predictors of postoperative Crohn's disease recurrence. Ileocolonoscopy is the only modality to detect mucosal recurrence after surgery; however, surrogate markers of inflammation, specifically stool lactoferrin and calprotectin as well as small intestine contrast ultrasound, are promising. Due to the high rate of surgery for the treatment of complications of Crohn's disease, prevention of postoperative disease has received considerable attention. Recent studies of azathioprine/6-mercaptopurine, nitroimidazole antibiotics, and infliximab have broadened the spectrum of medication options postoperatively.. Smoking cessation and ileocolonoscopy for early detection of Crohn's disease recurrence should be part of any postoperative management strategy. The selection of medication and optimal time to initiate treatment after surgery is less certain. Postoperative immunomodulators and antitumor necrosis factor agents may prevent Crohn's disease in those at high risk for recurrence. Treatment of patients by predictors of recurrence and personalization of management based on genotypes/phenotypes will be the focus of future study.

Topics: Anti-Inflammatory Agents; Colonoscopy; Crohn Disease; Endosonography; Feces; Gastrointestinal Agents; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Postoperative Complications; Recurrence; Risk Factors; Smoking; Time Factors

The definition of remission in Crohn's disease and ulcerative colitis has evolved to include mucosal healing as a measure of treatment efficacy. Randomized, controlled trials have demonstrated mucosal healing is attainable with the current arsenal of therapies available to treat inflammatory bowel disease. Mucosal healing has been shown to reduce the likelihood of clinical relapse, reduce the risk of future surgeries, and reduce hospitalizations. This review focuses on the latest studies addressing clinical outcomes of mucosal healing in the clinical trial and practice setting.

Topics: Adalimumab; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Colitis, Ulcerative; Crohn Disease; Endoscopy, Gastrointestinal; Feces; Humans; Infliximab; Intestinal Mucosa; Lactoferrin; Leukocyte L1 Antigen Complex

Inflammatory bowel disease (IBD), which includes ulcerative colitis, Crohn's disease, and indeterminate colitis, is characterized by chronic inflammation of the digestive tract and has a significant impact on quality of life. Coupled with clinical history, physicians rely on invasive tests (e.g. endoscopy and radiologic examinations) to diagnose IBD. Patients with other gastrointestinal illnesses (e.g. irritable bowel syndrome and celiac disease) may present with symptoms similar to those of an IBD patient. Therefore, a need exists for rapid and noninvasive measures to indicate the presence of IBD. The identification of potential biomarkers associated with IBD has expanded rapidly in the past decade. This article reviews the role of recently studied serologic and fecal markers in the diagnosis of IBD, and differentiation between subtypes of IBD.

Topics: Algorithms; Antibodies, Anti-Idiotypic; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Colitis, Ulcerative; Crohn Disease; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Polysaccharides; Saccharomyces cerevisiae; Sensitivity and Specificity

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

Fecal biomarkers are used increasingly to monitor Crohn's disease (CD). However, the relative accuracy of different markers in identifying inflammation has been poorly evaluated. We evaluated fecal calprotectin (FC), lactoferrin (FL), and S100A12 (FS) using endoscopic validation in a prospective study of the progression of CD after intestinal resection.. Data were collected from 135 participants in a prospective, randomized, controlled trial aimed at preventing postoperative CD recurrence. Three hundred nineteen stool samples were tested for FC, FL, and FS preoperatively and 6, 12, and 18 months after resection. Colonoscopy was performed at 6 and/or 18 months. Endoscopic recurrence was assessed blindly using the Rutgeerts score. C-reactive protein (CRP) and Crohn's Disease Activity Index (CDAI) were assessed.. FC, FL, and FS concentrations were elevated preoperatively (median: 1347, 40.9, and 8.4 μg/g, respectively). At 6 months postoperatively, marker concentrations decreased (166, 3.0, 0.9 μg/g) and were higher in recurrent disease than remission (275 versus 72 μg/g, P < 0.001; 5.7 versus 1.6 μg/g, P = 0.007; 2.0 versus 0.8 μg/g, P = 0.188). FC > 135 μg/g, FL > 3.4 μg/g, and FS > 10.5 μg/g indicated endoscopic recurrence (score ≥ i2) with a sensitivity, specificity, and negative predictive value (NPV) of 0.87, 0.66, and 91%; 0.70, 0.68, and 81%; 0.91, 0.12, and 71%, respectively. FC and FL correlated significantly with the presence and severity of endoscopic recurrence, whereas FS, CRP and CDAI did not.. FC was the optimal fecal marker for monitoring disease activity in postoperative CD and was superior to CRP and CDAI. FL offered modest sensitivity for detecting recurrent disease, whereas S100A12 was sensitive but had low specificity and NPV.

Topics: Adult; Biomarkers; C-Reactive Protein; Colonoscopy; Crohn Disease; Disease Progression; Endoscopy; Feces; Female; Follow-Up Studies; Humans; Inflammation; Inflammation Mediators; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Postoperative Period; Prognosis; Prospective Studies; Recurrence; Remission Induction; Severity of Illness Index

The glycoprotein lactoferrin is found in many body fluids but also in the granules of neutrophilic granulocytes. Fecal lactoferrin levels increase quickly with the influx of leukocytes into the intestinal lumen during inflammation. This biomarker has recently been shown to be a sensitive and specific marker of disease activity in chronic inflammatory bowel disease. Our aim was the determination of fecal lactoferrin as a marker of intestinal inflammation and therapeutic response following infliximab therapy in pediatric patients with Crohn's disease (CD). A total of five patients (ages 10-15 years) with severe Crohn's disease as defined by the Pediatric Crohn's Disease Activity Index (PCDAI) was enrolled in the study. The fecal lactoferrin levels were determined before and after therapy with infliximab by a quantitative lactoferrin ELISA (IBD-SCAN; TechLab, Inc.). Of the five patients on infliximab therapy, three received a single infusion and the remaining two underwent a regime with three maintenance infusions. All five patients responded to infliximab clinically after the first infusion, and in all patients, fecal lactoferrin levels significantly and rapidly decreased from elevated to near baseline in parallel to clinical assessment and the PCDAI. The reduction in fecal lactoferrin at days 7-10 was 93.43 +/- 4.49%, in comparison with the level before infliximab therapy, and correlated with a mean decrease in the PCDAI from 48.50 to 14.0. For the patients followed during multiple infusions, one remained with mild disease and the other reached remission (subjective and PCDAI). Fecal lactoferrin is a sensitive and specific biomarker representing intestinal inflammation and response to therapy in pediatric patients with Crohn's disease. It may be a helpful noninvasive diagnostic tool for monitoring therapeutic efficiency in pediatric IBD patients. Future studies are needed to further establish the relationship between endoscopic changes and the level of fecal lactoferrin as well as the possible role of lactoferrin as being an early and preclinical indicator of relapse.

Topics: Adolescent; Antibodies, Monoclonal; Child; Crohn Disease; Feces; Female; Follow-Up Studies; Gastrointestinal Agents; Humans; Infliximab; Lactoferrin; Male; Sensitivity and Specificity; Severity of Illness Index; Time Factors; Treatment Outcome

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

Topics: Administration, Oral; Animals; Antineoplastic Agents; Cattle; Colonic Neoplasms; Crohn Disease; Disease Models, Animal; Inflammation; Lactoferrin; Male; Mice; Mice, Inbred C57BL

The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations.. We analyzed FCP, LCT, and nCD64 before and after IFX induction in a pediatric Crohn's disease (CD) cohort study. Week-14 FCP biomarker remission was defined as FCP <250 µg/g, with clinical response defined as a weighted Pediatric Crohn's Disease Activity Index <12.5 or Δ>17.5 improvement. Predictive outcomes were calculated by receiver operating characteristics (ROCs).. Among 56 CD patients, ROC analysis identified an infusion 4 LCT <8.06 (area under the receiver operator characteristics [AUROC], 0.934, P < 0.001) and nCD64 <6.12 (AUROC, 0.76, P = 0.02) as the ideal cut points for week-14 FCP biomarker remission. End of induction IFX-trough of >9.4 µg/mL (AUROC, 0.799, P = 0.002) and >11.5 µg/mL (AUROC, 0.835, P = 0.003) were associated with a FCP <250 and FCP <100, respectively. We found patients achieving end of induction trough >5 µg/mL had a median FCP improvement (dose 1 to dose 4) of 90% compared with a median of 35% with levels <5 µg/mL (P = 0.024) with a similar median reduction in nCD64 (48% vs 20%, P = 0.031).. This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy. Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.

Topics: Biomarkers; Child; Cohort Studies; Crohn Disease; Feces; Gastrointestinal Agents; Humans; Infliximab; Lactoferrin; Leukocyte L1 Antigen Complex; Neutrophils; Receptors, IgG; Reference Values

Fecal lactoferrin (FL) levels may mirror drug-induced changes in inflammation in ulcerative colitis and Crohn disease in a timely way and could be used to assess loss of response (LOR) to biologics.. This study is a retrospective outcome review in 61 patients on adalimumab, infliximab, or vedolizumab managed in our center and followed for 6 to 24 months. Patients were 1) in clinical remission or 2) were experiencing possible LOR.. For group 1, in 71% of 31 patients, FL slowly increased during the therapeutic interval (R2 = 0.769; P < 0.001), thus reflecting increasing inflammation as drug concentrations decreased. In the remaining patients, FL was undetectable throughout the therapeutic interval because of a stronger suppression of inflammation. For group 2, in 30 patients negative for infections, FL levels measured 1 to 3 days after infusion/injection compared to preadministration values either increased (nonresponders)-in these patients the medication was switched to another class; partially decreased (partial responders)-the therapeutic interval was shortened; or were normal throughout (responders)-causes for symptoms unrelated to disease activity were found for all. After FL-based management, 3-month standardized clinical scores were normalized in both partial responders (0.58 ± 0.21 vs 0.13 ± 0.09; P < 0.001) and nonresponders (0.81 ± 0.17 vs 0.12 ± 0.08; P < 0.001), and FL levels dropped by up to 99%.. Levels of FL reflect drug-induced changes in mucosal inflammation in a timely way, thus enabling rapid assessment of therapeutic response in patients with ulcerative colitis and with Crohn disease. In patients with suspected LOR, FL levels before and after infusion/injection accurately separated responders, partial responders, and nonresponders. The strategy proposed here is simple, accurate, and easily applicable to clinical practice.

Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Gastrointestinal Agents; Humans; Inflammation; Infliximab; Lactoferrin; Retrospective Studies

In Crohn's disease (CD) a small bowel study-in addition to colonoscopy-is considered necessary for diagnosis/staging. In this study we re-examined the role of capsule endoscopy (CE), colonoscopy, imaging tests [magnetic resonance enterography/computed tomographic enterography (MRE/CTE)], and inflammatory markers [fecal lactoferrin and C-reactive protein (FL/CRP)] in CD patients who had undergone intestinal resection and in those who never had surgery.. In this retrospective study 43 consecutive patients underwent CE because of staging/symptoms unexplained by colonoscopy/imaging. We compared colonoscopy, imaging, and FL/CRP with CE and evaluated the impact of the latter on clinical management and outcomes.. In patients who never had surgery imaging was negative with a positive CE in 8/15 (53%) of cases. Colonoscopy was insufficient for disease staging in 10/20 (50%) cases. CRP and FL were normal with a positive CE in 35% and 28% of cases, respectively. CE findings changed the management in 6/20 (30%) of cases, with 83% showing clinical/biochemical improvement after up to 15 months of follow-up. In postoperative patients CE was positive with negative imaging in 6/8 (75%) cases. Colonoscopy was insufficient for disease staging in 13/22 (59%) cases. CRP and FL were normal in 42% and 31.8% of patients with positive CE. In these patients CE findings changed the management in 12/23 (52%) cases with 83% of them showing clinical/biochemical improvement after up to 18 months of follow-up.. Omitting CE from diagnostic/staging algorithms in CD tends to underdiagnose clinically significant small bowel lesions, thus impacting on patients' management and outcomes. 10.1093/ibd/izy048_video1izy048.video15794820403001.

Topics: Adult; C-Reactive Protein; Capsule Endoscopy; Colonoscopy; Crohn Disease; Feces; Female; Humans; Intestine, Small; Lactoferrin; Magnetic Resonance Imaging; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Tomography, X-Ray Computed

Difficulties in diagnosis of inflammatory bowel disease (IBD) motivate the search for new diagnostic tools, including laboratory tests. The aim of this study was to evaluate concentrations of the neutrophil (NEU) proteins leukocyte elastase (HLE-α1AT), lactoferrin and calprotectin as potential biomarkers used in the diagnosis and assessment of clinical activity of Crohn's disease (CD) and ulcerative colitis (UC).. The study included 27 patients with CD, 33 patients with UC and 20 healthy controls. Plasma concentrations of calprotectin, lactoferrin and HLE-α1AT were measured using ELISA.. In patients with CD higher concentrations of HLE-α1AT (64.3±43.1 vs. 30.1±7.7 ng/l, P<0.001), calprotectin (151.6±97.8 vs. 69.9±22.1 ng/l, P<0.001) and lactoferrin (243.2±102.0 vs. 129.7±32.7 ng/l, P<0.001) than in the control group were found. In patients with UC higher plasma concentrations of HLE-α1AT (62.0±30.9 vs. 30.1±7.7 ng/l, P<0.001), calprotectin (149.6±72.3 vs. 69.9±22.1 ng/l, P<0.001) and lactoferrin (242.6±107.5 vs 129.7±32.7 ng/l, P<0.001) than in the control group were found. HLE-α1AT/NEU and lactoferrin/NEU ratios in patients with UC were significantly higher compared with patients with CD. Calprotectin (P=0.010) and lactoferrin (P=0.023) levels were higher in patients with the active compared with inactive phase of CD.. The diagnostic characteristics of plasma granulocyte protein concentrations indicate the usefulness of these tests in the diagnosis of IBD. Higher HLE-α1AT and lactoferrin/NEU ratios in patients with UC than with CD may suggest the usefulness of these ratios in differential diagnostics. Plasma calprotectin and lactoferrin levels may be useful in CD activity assessment.

Topics: Biomarkers; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Neutrophils

Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn's disease (CD). Conventional parameters poorly assess CD remission, and although fecal biomarkers assess colonic activity, their role in assessing remission is uncertain. We report CE findings in small-bowel CD patients in clinical remission compared with fecal biomarkers and standard clinical tools to determine mucosal remission and predict relapses.. Forty-three adult small-bowel CD patients in clinical remission (Crohn's Disease Activity Index [CDAI] <150) were prospectively enrolled at 4 academic centers and followed clinically for 12 months. Baseline CE studies were scored using the Capsule Endoscopy Scoring Index (CESI or Lewis score). Baseline and endpoint fecal biomarkers were assayed.. CE findings were normal in 17 patients (40%), mild inflammation in 19 (44%), and moderate to severe inflammation in 7 (16%). Of the 26 patients (60%) with mucosal inflammation on CE, 85% had elevated baseline fecal calprotectin and 77% elevated lactoferrin level. Calprotectin and lactoferrin were normal in all patients without inflammation and elevated in all with moderate to severe inflammation. CESI correlated significantly with calprotectin, lactoferrin, and S100A12 levels but not either CDAI or C-reactive protein. During follow-up, 14% of patients exhibited a clinical flare; all had mucosal inflammation at CE and 83% had elevated baseline calprotectin and lactoferrin levels.. In small-bowel CD patients in clinical remission, many had ongoing mucosal inflammation assessed by CE and fecal biomarkers. Only some developed a clinical flare during medium-term follow-up. These findings suggest CE and fecal biomarkers are useful in monitoring small-bowel CD progress.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Capsule Endoscopy; Crohn Disease; Feces; Female; Humans; Intestine, Small; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Remission Induction; ROC Curve; S100A12 Protein; Severity of Illness Index; Symptom Flare Up

To evaluate the accuracy and best cut-off value of fecal calprotectin (FC) and fecal lactoferrin (FL) to predict disease recurrence in asymptomatic patients presenting with anastomotic strictures.. This was a longitudinal single tertiary center study based on prospectively collected data (recorded in a clinical database created for this purpose) performed between March 2010 and November 2014. Crohn's disease (CD) patients with anastomotic stricture who submitted to postoperative endoscopic evaluation were included. Stools were collected on the day before bowel cleaning for FC and FL. Endoscopic balloon dilation (EBD) was performed if the patient presented an anastomotic stricture not traversed by the colonoscope, regardless of patients' symptoms. Successful dilation was defined as passage of the colonoscope through the dilated stricture into the neotermimal ileum. Postoperative recurrence was defined as a modified Rutgeerts score of ≥ i2b.. Fecal markers are good predictors of CD endoscopic recurrence in patients with asymptomatic anastomotic stricture. FC and FL may guide the need for EBD in this context.

Topics: Adult; Anastomosis, Surgical; Biomarkers; Catheterization; Colectomy; Colon; Colonoscopes; Colonoscopy; Constriction, Pathologic; Crohn Disease; Dilatation; Feces; Female; Humans; Ileum; Lactoferrin; Leukocyte L1 Antigen Complex; Longitudinal Studies; Male; Middle Aged; Postoperative Period; Prospective Studies; Recurrence

Capsule endoscopy (CE) is often used to investigate small bowel Crohn's disease (CD).. The aim of this study is to prospectively assess the value of fecal calprotectin and lactoferrin to predict CE findings.. Sixty-eight consecutive patients that were referred for CE were included. Stool samples for calprotectin and lactoferrin and blood samples were collected for relevant parameters. Correlation between fecal markers and CE findings was assessed and receiver operating characteristic (ROC) curves were built to determine the predictive values of fecal markers for the diagnosis of CD.. Fecal calprotectin data was available for all the patients and lactoferrin data for 38. CE findings compatible with CD were found in 23 (33%) patients and 45 (67%) were negative for CD. The average age of the CD group was 34 compared to 46 in the non-CD group (p = .048). Median calprotectin and lactoferrin in the CD group and in the control group were 169 mg/kg vs. 40 (p = .004) and 6.6 mg/kg vs. 1 (p = .051), respectively. The area under the ROC curve was 0.767 for calprotectin and 0.70 for lactoferrin. A fecal calprotectin concentration of 95 mg/kg and fecal lactoferrin of 1.05 mg/kg had a sensitivity, specificity, positive predictive value and negative predictive value of 77 and 73%, 60 and 65%, 50 and 50%, and 84 and 84% in predicting CE findings compatible with CD.. Fecal markers are simple and noninvasive surrogates for predicting CE findings compatible with CD. Fecal markers can help determine which patients should be referred for CE. ClinicalTrials.gov Identifier: NCT01266629.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Capsule Endoscopy; Child; Child, Preschool; Crohn Disease; Feces; Female; Humans; Israel; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Prospective Studies; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Young Adult

A 22-year-old male suffering from abdominal pain, repeated diarrhea, and weight loss visited the Digestive Disease Department of Nagoya City University Hospital on 19 December 2011. He was hospitalized and diagnosed with Crohn's colitis. His Crohn's Disease Activity Index (CDAI) was 415. Treatment by granulocyte apheresis, mesalazine, and adalimumab was started. His CDAI was 314 on 30 December and 215 on 5 January. A colonoscopic examination on 19 January showed almost complete remission in the transverse colon and marked remission in the rectum. Mesalazine therapy was stopped on 28 February, and the patient was instructed to self-inject 40 mg of adalimumab every other week. His CDAI was 50 on 10 April, indicating clinical remission. His last self-injection of adalimumab was on 24 April 2012, and he started taking 1 g of bovine lactoferrin (bLF) daily. His CDAI was 35 on 8 January 2013. He continued taking 1 g of bLF daily without any other treatment for Crohn's disease. Laboratory blood tests on 7 September 2015 showed no sign of disease recurrence, and a colonoscopic examination on 23 October 2015 showed almost complete mucosal healing. This case indicates that ingestion of bLF to maintain Crohn's disease in a remissive state should be further explored.

Topics: Adult; Animals; Anti-Infective Agents; Cattle; Crohn Disease; Humans; Lactoferrin; Male; Prognosis; Young Adult

Increasing numbers of patients with inflammatory bowel disease (IBD) have raised the need for a rapid noninvasive means to monitor disease activity. We validated two rapid tests for faecal calprotectin and one for faecal lactoferrin and compared them to the most common clinical and endoscopic scores, enzyme-linked immunosorbent assay (ELISA) calprotectin test and systemic inflammation markers.. The clinical and endoscopic disease activity of 72 patients with colonic IBD, who underwent ileocolonoscopy, was determined. The patients provided stool samples to measure calprotectin and lactoferrin, and blood samples to measure systemic inflammation markers.. Rapid calprotectin tests correlated significantly with clinical and endoscopic indices and standard ELISA calprotectin in ulcerative colitis, but not in Crohn's disease. CalDetect correlated more closely with ELISA calprotectin than CerTest FC in concentrations exceeding 200 μg/g. CalDetect was also more sensitive in indicating histological remission or mild disease than was CerTest FC at cut-off of 200 μg/g. CerTest Lactoferrin was comparable to CalDetect in their correlation with clinical, endoscopic and histological scores.. These rapid tests are suitable for identifying patients with inactive or mildly active disease, but as semiquantitative or qualitative tests, they cannot totally replace ELISA calprotectin in decision-making related to therapy.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Colitis, Ulcerative; Colonoscopy; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Feces; Female; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Point-of-Care Testing; ROC Curve; Sensitivity and Specificity; Young Adult

Endoscopic recurrence after surgery for Crohn's disease (CD) is high, and it has important prognostic value. Crohn's disease will recur in the majority of patients after surgery. Fecal calprotectin (FC) and lactoferrin (FL) have attracted interest in the postoperative setting for predicting relapse. We have evaluated the accuracy of FC and FL in diagnosing endoscopic recurrence (ER) using the modified Rutgeerts score (MRS) compared with the Rutgeerts score (RS).. A series of consecutive patients who underwent ileocolonic resection for Crohn's disease were evaluated. Biomarkers, clinical indexes, and fecal markers were recorded on the day of ileocolonoscopy. ER was defined as a MRS ≥ i2b or a RS ≥ i2.. Ninety-nine patients were included in this prospective cohort. The median time between surgery and colonoscopy was 87.5 months (IQR, 31-137). FC and FL levels were higher in patients with ER than in those in remission (Median FC, 196.5 μg/g [IQR, 96-634 μg/g] versus 42.1 μg/g [IQR 19-91.60 μg/g; P < 0.001]; Median FL, 23.27 μg/g [IQR 8.9-47.8 μg/g] versus 2 μg/g [IQR 0.9-7.26 μg/g; P < 0.001]). Using the MRS, 34% of patients presented with ER compared with 76% if the RS was used. The RS performed worse than the MRS with a decrease in sensitivity (74% versus 48% for FC and 85% versus 55% for FL) and in NPV (91% versus 33% for FC, and 90% versus 37% for FL). Furthermore, the accuracy of the MRS was higher than that of the RS (75% versus 55%).. Both FC and FL proved to correlate well with endoscopic findings in the evaluation of Crohn's disease after surgery. Both markers predicted recurrence with greater accuracy when the MRS was used. Fecal markers can be used to monitor disease recurrence after intestinal resection, with patients being selected to undergo further endoscopic evaluation.

Topics: Adult; Biomarkers; Colonoscopy; Crohn Disease; Databases, Factual; Feces; Female; Follow-Up Studies; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Portugal; Postoperative Period; Prognosis; Prospective Studies; Recurrence; Remission Induction; ROC Curve

Diagnosis and monitoring of Crohn's disease (CD) is difficult and time-consuming. In recent years, diagnostic usefulness of fecal calprotectin has been proven. However, data on the utility of other fecal markers are scarce.. To evaluate the usefulness of fecal lactoferrin (FL) in the assessment of CD activity.. The group consisted of 101 CD patients (median age: 30 years, IQR: 24-37). FL was measured in a single stool sample by using the immunoenzymatic methods. The clinical activity of the disease was evaluated by using the Crohn's Disease Activity Index (CDAI). Depending on the location of the disease, either a colonoscopy or magnetic resonance enterography was performed or both in order to evaluate the disease activity by using appropriate endoscopic and enterographic scores.. Median FL concentration was 84.14 (IQR: 36.4-302.9) μg/ml and it correlated with C-reactive protein concentration (p=0.0000001, r=0.5), CDAI (p=0.002, r=0.3) and colonic Simple Endoscopic Score for Crohn's Disease (SES-CD) (p=0.000004, r=0.5). Assuming endoscopic remission in the large intestine with colonic SES-CD≤3 points, a ROC curve showed that FL concentration of 145.82 μg/ml had 84.6% sensitivity and 60.5% specificity in discriminating CD patients with endoscopically active and inactive disease [AUC: 0.676 (95% CI: 0.531-0.8), (p=0.0347)]. The positive predictive value for this concentration was 42% and negative predictive value -92%.. FL is a sensitive marker of CD activity and it reliably reflects the mucosal inflammatory lesions in large intestine. Thus, it can be helpful in diagnostics and monitoring of CD.

Topics: Adolescent; Adult; Biomarkers; Colon; Crohn Disease; Feces; Female; Humans; Intestinal Mucosa; Lactoferrin; Male; Sensitivity and Specificity; Young Adult

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

Crohn's disease is a multifactorial disease in which an aberrant immune response to commensal intestinal microbiota leads to chronic inflammation. The small intestine of patients with Crohn's disease is colonized by a group of adherent-invasive Escherichia coli strongly able to adhere and invade intestinal epithelial cells lactoferrin is an iron-binding glycoprotein known to have anti-bacterial and anti-inflammatory activities.. We explore the ability of bovine lactoferrin to modulate the interactions between the adherent-invasive E. coli strain LF82 and intestinal epithelial cells as well as the inflammatory response.. Bacterial adhesion and invasion assays were used to assess the antimicrobial activity of lactoferrin. Electron microscopy was used to characterize bacteria-cell interactions. The mRNA expression of pro-inflammatory cytokines was measured both in cultured cells and in biopsies taken from intestine of patients affected by Crohn's disease.. Lactoferrin inhibited bacterial invasion through minimally affecting adhesion. This divergence was due to a mannose-dependent lactoferrin binding to the bacterial type 1 pili and consequent bacterial aggregation on the intestinal epithelial cell surface. Expression of pro-inflammatory cytokines, such as TNF-alpha, IL-8, and IL-6, was markedly inhibited by lactoferrin both in cultured and Crohn-derived intestinal cells.. Bovine lactoferrin might function via an antibacterial and/or anti-inflammatory mechanism in the treatment of Crohn's disease.

Topics: Animals; Anti-Infective Agents; Bacterial Adhesion; Caco-2 Cells; Cattle; Crohn Disease; Escherichia coli; Escherichia coli Infections; Gene Expression; Humans; Interferon-gamma; Interleukin-6; Interleukin-8; Intestinal Mucosa; Lactoferrin; Mannose; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Receptors, Immunologic; RNA, Messenger; Tumor Necrosis Factor-alpha

Conflicting data are reported on pro- or anti-inflammatory activity of bovine lactoferrin (bLf) in different cell models as phagocytes or epithelial cell lines infected by bacteria. Here we evaluated the bLf effect on epithelial models mimicking two human pathologies characterized by inflammation and infection with specific bacterial species. Primary bronchial epithelium from a cystic fibrosis (CF) patient and differentiated intestinal epithelial cells were infected with Pseudomonas aeruginosa LESB58 isolated from a CF patient and Adherent-Invasive Escherichia coli LF82 isolated from a Crohn's disease patient. Surprisingly, bLf significantly reduced the intracellular bacterial survival, but differently modulated the inflammatory response. These data lead us to hypothesize that bLf differentially acts depending on the epithelial model and infecting pathogen. To verify this hypothesis, we explored whether bLf could modulate ferroportin (Fpn), the only known cellular iron exporter from cells, that, by lowering the intracellular iron level, determines a non permissive environment for intracellular pathogens. Here, for the first time, we describe the bLf ability to up-regulate Fpn protein in infected epithelial models. Our data suggest that the mechanism underlying the bLf modulating activity on inflammatory response in epithelial cells is complex and the bLf involvement in modulating cellular iron homeostasis should be taken into account.

Topics: Animals; Antimicrobial Cationic Peptides; Bronchi; Cation Transport Proteins; Cattle; Cells, Cultured; Crohn Disease; Cystic Fibrosis; Epithelial Cells; Escherichia coli; Humans; Inflammation Mediators; Iron; Lactoferrin; Models, Biological; Pseudomonas aeruginosa; Respiratory Mucosa

Topics: Biomarkers; Colitis, Ulcerative; Crohn Disease; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Point-of-Care Systems; Pyruvate Kinase; Reference Values; S100 Proteins; S100A12 Protein; Severity of Illness Index

The use of fecal markers to monitor Crohn's disease is crucial for assessing the response to treatment.. To assess the inflammatory activity of Crohn's disease by comparing fecal markers (calprotectin and lactoferrin), colonoscopy combined with biopsy, and the Crohn's disease activity index (CDAI), as well as serum markers, before treatment with infliximab, after the end of induction, and after the end of maintenance.. Seventeen patients were included who had been previously diagnosed with Crohn's disease and were using conventional treatment but required the introduction of biological therapy with infliximab. Each patient underwent a colonoscopy with biopsy, serum, and fecal (calprotectin and lactoferrin) tests to assess inflammatory activity, and CDAI assessments before treatment with infliximab, after induction (week 8), and after maintenance (week 32).. The calprotectin levels exhibited significant reductions (P=0.04) between the assessment before treatment with infliximab and the end of induction, which did not occur after the end of the maintenance phase. Lactoferrin remained positive throughout the three phases of the study. Regarding the histological assessment, a significant difference was found only between the assessment before treatment and after the end of maintenance (P=0.036), and 60% of the patients exhibited histological improvements after the completion of the follow-up period. The CDAI exhibited a significant difference between the assessment before treatment with infliximab and after induction, as well as before treatment and after maintenance (P<0.01).. Calprotectin and lactoferrin are not useful for monitoring inflammatory activity in Crohn's disease patients who are subjected to biological therapy.

Topics: Adult; Antibodies, Monoclonal; Biological Therapy; Biomarkers; Biopsy; C-Reactive Protein; Colonoscopy; Crohn Disease; Feces; Female; Gastrointestinal Agents; Humans; Infliximab; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Predictive Value of Tests; Prognosis; Severity of Illness Index; Treatment Outcome

Fecal lactoferrin is the direct expression of intestinal inflammation in Crohn's disease (CD). The aim of this study was to analyze the in vivo intimate correlation between intestinal and systemic inflammation in CD patients in clinical remission following bowel resection. The secondary end point was to evaluate the prognostic value of lactoferrin levels and serum cytokines in terms of need of surgery for recurrence in these patients.. Fecal lactoferrin and serum cytokine (interleukin (IL)-1beta, IL-6, IL-12, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta1) levels were assessed; hematological and biochemical investigations were carried out, and Crohn's Disease Activity Index was evaluated in the 36 patients who had undergone bowel resection. The prognostic value of lactoferrin and cytokine levels in terms of surgical recurrence was assessed by re-calling patients after 24 months from the enrolment in the study.. All patients, evaluated after a follow-up of 36 +/- 5 months, were in clinical remission. Fecal lactoferrin levels were found to be significantly correlated with IL-6 (R = 0.431, p = 0.025) and C-reactive protein (CRP; R = 0.507, p = 0.007), while no correlation was observed between lactoferrin and IL-1beta, IL-12, TNF-alpha, or TGF-beta1. Reoperation for anastomotic recurrence tended to occur significantly more frequently in patients with higher IL-6 (p = 0.10).. Subclinical intestinal inflammation, expressed by fecal lactoferrin, seems to keep the systemic inflammation alive in CD patients through the IL-6-CRP cascade. IL-6 seems to be predictive of the outcome of CD patients undergoing surgery.

Topics: Adult; Biomarkers; C-Reactive Protein; Colon; Crohn Disease; Feces; Female; Humans; Ileum; Inflammation; Interleukin-12; Interleukin-1beta; Interleukin-6; Lactoferrin; Male; Middle Aged; Prognosis; Recurrence; Transforming Growth Factor beta1

Serial monitoring data for faecal calprotectin and lactoferrin during Crohn's disease (CD) therapy are scarce. The aim of this research was to study the behaviour of faecal biomarkers during CD therapy.. Adult CD patients (n = 19) needing therapy enhancement were prospectively recruited. The simple endoscopic score for Crohn's disease (SES-CD) was administered before and 4-6 months after therapy. At baseline and at 2-3 and 4-6 months, patients provided faecal samples for measurements of calprotectin and lactoferrin.. Of 19 patients, seven were endoscopic responders, three were partial responders and nine were non-responders. During therapy, both faecal-biomarker concentrations decreased significantly in responders: median calprotectin from 1282 microg/g (range 156-2277 microg/g) to 73 microg/g (range 7-2222; P = 0.005) and lactoferrin from 233 microg/g (range 2.8-802 microg/g) to 0.0 microg/g (range 0.0-420 microg/g; P = 0.005), and these changes correlated significantly with changes in the SES-CD. In non-responders, changes in faecal biomarkers were non-significant: calprotectin decreased from 1017 microg/g (range 53-3928 microg/g) to 223 microg/g (range 35-15330 microg/g; P = 0.594) and lactoferrin from 22.5 microg/g (range 2.1-629 microg/g) to 13.0 microg/g (range 3.5-1259 microg/g; P = 0.515).. The faecal neutrophil-derived proteins calprotectin and lactoferrin are reliable surrogate markers of mucosal improvement. Endoscopic responders achieved normalization of faecal biomarkers, whereas in the majority of endoscopic non-responders these markers remained abnormal.

Topics: Adult; Biomarkers; Colonoscopy; Crohn Disease; Feces; Female; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Severity of Illness Index

Fecal lactoferrin (FL) is a noninvasive biomarker that is elevated in Crohn disease (CD) compared to irritable bowel syndrome. The purpose of this study was to evaluate FL in identifying children with active versus inactive CD.. Fresh stool samples were collected from children with CD scheduled for endoscopy or a clinic visit, and from new outpatients who were scheduled for colonoscopy. FL was determined using a polyclonal antibody-based enzyme-linked immunosorbent assay. Physical global assessment, endoscopic findings, erythrocyte sedimentation rate (ESR), and the Pediatric CD Activity Index (PCDAI) were recorded for patients with CD. The PCDAI scores symptoms, laboratory parameters, physical examination, and extraintestinal manifestations. A score of ≤10 is inactive disease, 11 to 30 is mild active, and ≤31 is moderate to severe active.. Of 101 study patients (4- to 20-year-old, 66 boys), 31 had active CD, 23 had inactive CD, and 37 had noninflammatory bowel disease (non-IBD) conditions. Four patients with ulcerative colitis and 6 patients with polyposis were excluded from analysis. FL was significantly elevated in CD versus non-IBD (P < 0.001) and in active versus inactive CD (P < 0.001). The PCDAI and ESR were higher in active CD than in inactive CD (both P < 0.001). Using an FL cutoff of 7.25 μg/g, FL has 100% sensitivity and 100% negative predictive value in detecting active CD. Using an FL cutoff level of 60 μg/g, FL had 84% sensitivity, 74% specificity, 81% positive predictive value, and 77% negative predictive value for detecting active CD.. FL is a promising biomarker of active CD and may be more practical to use when it is not feasible to obtain all of the necessary clinical information for the PCDAI.

Topics: Adolescent; Adult; Biomarkers; Child; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Feces; Female; Humans; Intestinal Diseases; Lactoferrin; Male; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Young Adult

Capsule endoscopy has been shown to be useful in diagnosing small bowel Crohn's disease. Faecal lactoferrin has been shown to have a high sensitivity and specificity in discriminating between inflammatory bowel disease and irritable bowel syndrome. There have been no studies on the use of faecal lactoferrin in the setting of suspected Crohn's disease using capsule endoscopy. Our aim was to investigate the clinical utility of lactoferrin in patients with suspected Crohn's disease using capsule endoscopy.. Data was collected prospectively on patient symptoms, family history and blood parameters. Patients were requested to return a stool sample and quantitative analysis using sandwich ELISA was performed for faecal lactoferrin.. Seventeen patients were recruited with all patients having had more than one criterion for referral. The diagnostic yield for capsule endoscopy was 41%, of which 71% of patients had an elevated faecal lactoferrin (correlation coefficient 0.56, p=0.01). The sensitivity, specificity, positive predictive value and negative predictive value of faecal lactoferrin were 71%, 100%, 100% and 83%, respectively.. Faecal lactoferrin has a high positive and negative predictive value for the diagnosis of small bowel Crohn's disease, detected by capsule endoscopy. Faecal lactoferrin is a useful marker (in conjunction with clinical parameters) to determine which patients should be referred for capsule endoscopy.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Capsule Endoscopy; Crohn Disease; England; Enzyme-Linked Immunosorbent Assay; Feces; Female; Humans; Inflammation Mediators; Lactoferrin; Male; Middle Aged; Patient Selection; Pilot Projects; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity; Young Adult

Irritable bowel syndrome (IBS) is a highly prevalent functional disorder. According to the Rome criteria, macroscopic and histological inflammation is a crucial exclusion criterion for IBS. Human defensins appear to be part of the innate immune system in the gastrointestinal tract. Human beta-defensin-2 (HBD-2) was the first inducible human antimicrobial protein discovered. The expression is induced by probiotic microorganisms and proinflammatory cytokines. Recent results imply that HBD-2 is expressed in active intestinal inflammation, especially in ulcerative colitis (UC). Our aim was to evaluate fecal measurements of HBD-2 in patients with active UC and IBS, and in healthy controls (HCs).. Fecal specimens were collected from a total of 100 participants (30 with active UC, 46 IBS, and 24 HCs). Exclusion criteria were the current use of probiotics and antibiotics. Furthermore, IBS patients with elevated C-reactive protein or leukocytes, a history of bacterial overgrowth or infectious gastrointestinal disease over the last 6 month were excluded. Disease status was addressed in all participating subjects by medical history and current symptoms. In addition, each IBS and UC patient underwent ileocolonoscopy with histopathology. Fecal inflammation markers lactoferrin (Lf) and calprotectin (Cal) were measured by enzyme-linked immunosorbent assay (ELISA) and reported as microg/g. Fecal HBD-2 was measured by ELISA and reported as ng/g feces. In addition, immunoblots were performed for fecal HBD-2. Paraffin-embedded tissue from colonic biopsies was tested for HBD-2 peptides by immunohistochemistry.. Lf as well as Cal was elevated in active UC (mean: 152.1+/-s.d. 374.7 microg/g; 103.5+/-87.1 microg/g), compared with IBS (8.3+/-19.4 microg/g; 18.6+/-23.3 microg/g), and HCs (0.4+/-0.5 microg/g; 7.1+/-7.9 microg/g). Scheffe post hoc tests revealed significant differences (P=0.006; P<0.001) between active UC vs. IBS and HC. In contrast, HBD-2 levels were highest in active UC (mean: 106.9+/-s.d. 91.5 ng/g), almost as high in IBS (pts 76.0+/-67.9 ng/g), and lowest for HCs (29.9+/-16.1 ng/g). Scheffe post hoc tests revealed significant differences (P<0.001) between the groups of patients (UC and IBS) vs. HCs. Immunohistochemical investigation was consistent with fecal secretion data and demonstrated the presence of beta-defensin 2 peptides in colonic epithelial enterocytes in UC as well as IBS patients with elevated fecal HBD-2.. The results indicate significantly elevated levels of HBD-2 in patients with IBS compared with HCs and similar to those with active UC. The results support an activation of the mucosal innate defense system toward a proinflammatory response in IBS patients in the absence of macroscopic signs of inflammation.

Topics: Adolescent; Adult; Aged; beta-Defensins; Case-Control Studies; Colitis, Ulcerative; Colonoscopy; Crohn Disease; Feces; Humans; Immunity, Innate; Intestinal Mucosa; Lactoferrin; Leukocyte L1 Antigen Complex; Middle Aged; Young Adult

The purpose of the study was to determine the role of fecal calprotectin and lactoferrin in the prediction of inflammatory bowel disease relapses, both in patients with ulcerative colitis (UC) and Crohn's disease (CD), in a large, long-term, follow-up study.. The prospective multicenter study included CD and UC patients who had been in clinical remission for 6 months. At baseline, patients provided a single stool sample for calprotectin and lactoferrin determination. Follow-up was 12 months in patients showing no relapse and until activity flare in relapsing patients.. In all, 163 patients (89 CD, 74 UC) were included. Twenty-six patients (16%) relapsed during follow-up. Calprotectin concentrations in patients who suffered a relapse were higher than in nonrelapsing patients (239 +/- 150 versus 136 +/- 158 microg/g; P < 0.001). Relapse risk was higher in patients having high (>150 microg/g) calprotectin concentrations (30% versus 7.8%; P < 0.001) or positive lactoferrin (25% versus 10%; P < 0.05). Fecal calprotectin (>150 microg/g) sensitivity and specificity to predict relapse were 69% and 69%, respectively. Corresponding values for lactoferrin were 62% and 65%, respectively. The area under the receiver operating characteristic curve to predict relapse using calprotectin determination was 0.73 (0.69 for UC and 0.77 for CD). Better results were obtained when only colonic CD disease or only relapses during the first 3 months were considered (100% sensitivity). High fecal calprotectin levels or lactoferrin positivity was associated with clinical relapse in Kaplan-Meier survival analysis, and both fecal tests were associated with relapse in the multivariate analysis.. Fecal calprotectin and lactoferrin determination may be useful in predicting impending clinical relapse-especially during the following 3 months-in both CD and UC patients.

Topics: Adult; Biomarkers; Case-Control Studies; Colitis, Ulcerative; Crohn Disease; Feces; Female; Follow-Up Studies; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Prognosis; Prospective Studies; Recurrence; Remission Induction

Identifying Crohn's disease recurrence in symptomatic patients after ileocaecal resection is difficult. The aim of this study was to evaluate faecal concentrations of granulocyte degradation products in this setting.. A postoperative cohort of 13 patients was followed prospectively for 1 year with regular faecal calprotectin (FC) and lactoferrin (FL) measurements. A second postoperative cohort (median 24 months after resection) of 104 patients provided a single stool sample. Faecal measurements were compared with symptom diaries, the Harvey Bradshaw Index, endoscopic examination, C-reactive protein and platelet measurement.. In the uncomplicated course, both markers normalized within 2 months. Both FC and FL correlated significantly with Harvey Bradshaw Index (P < 0.001). Twenty-eight patients with severely clinically active disease had high mean(s.e.) levels of FC (661.1(119.1) microg/g) and FL (116.6(32.2) microg/g); and 43 with clinically inactive disease had low levels of FC (70.2(27.1) microg/g) and FL (5.9(2.4) microg/g). In patients with mild to moderately clinically active disease, FC and FL identified individuals with and without recurrent inflammatory disease. Faecal markers were more accurate at predicting clinical disease activity than C-reactive protein, platelet count or endoscopic appearance.. FC and FL are non-invasive tests that can help to identify disease recurrence in symptomatic postoperative patients.

Topics: Adolescent; Adult; Aged; Biomarkers; C-Reactive Protein; Crohn Disease; Epidemiologic Methods; Feces; Female; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Recurrence; Young Adult

Faecal calprotectin and lactoferrin increasingly serve as surrogate markers of disease activity in IBD. Data on the correlation of these markers with simple endoscopic score for Crohn's disease (SES-CD) and with histological findings are as yet limited. Aim To study the correlation of faecal calprotectin and lactoferrin with SES-CD and histology.. During 87 consecutive ileocolonoscopies, SES-CD was calculated and biopsy specimens were obtained from the ileum, colon and rectum. Faecal calprotectin and lactoferrin were measured.. In ileocolonic or colonic disease, both faecal calprotectin and lactoferrin correlated significantly with colon SES-CD (P < 0.001) and colon histology (P < 0.001). In patients with normal calprotectin or lactoferrin levels, endoscopic and histology scores were significantly lower than in those with elevated concentrations (P < 0.001). In ileal CD, ileal SES-CD correlated with histology (P < 0.001), but not with faecal calprotectin (P = 0.161) or lactoferrin (P = 0.448).. In ileocolonic and colonic disease, endoscopic score SES-CD and histological findings correlated significantly with faecal calprotectin and lactoferrin. A normal faecal-marker concentration was a reliable surrogate marker for endoscopically and histologically inactive CD. Ileal endoscopic score and histological findings failed, however, to correlate with faecal markers.

Topics: Adult; Aged; Biomarkers; Crohn Disease; Endoscopy, Gastrointestinal; Feces; Female; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Predictive Value of Tests; Severity of Illness Index; Statistics as Topic; Young Adult

The quantitative relationships between instruments and assays that measure clinical, endoscopic, and biologic disease activity in patients with Crohn's disease are poorly characterized. This study evaluated the correlations between the Crohn's Disease Activity Index (CDAI), the Simple Endoscopic Score for Crohn's Disease (SES-CD), serum high-sensitivity C-reactive protein (hsCRP) (both phenotype and genotype) and interleukin-6 (IL-6), and fecal calprotectin and lactoferrin.. A total of 164 patients with Crohn's disease undergoing colonoscopy were enrolled. The CDAI and SES-CD scores, serum hsCRP and IL-6, CRP and IL-6 genotypes, and fecal calprotectin and lactoferrin were measured.. There were no significant associations between the CDAI and SES-CD scores (Spearman rank correlation coefficient, 0.15) or between the CDAI scores and the serum concentrations of hsCRP and IL-6, or the fecal concentrations of calprotectin and lactoferrin. In contrast, the serum hsCRP and IL-6 concentrations and the fecal calprotectin and lactoferrin concentrations were significantly higher in patients with more severe endoscopic disease activity (SES-CD score > 7 points) (P < .001 for all comparisons). The CRP 717 mutant homozygote and heterozygote status was associated with significantly lower concentrations of hsCRP (P = .02). There was a trend toward higher hsCRP concentrations in the CRP 286 heterozygous adenine mutant-type mutant genotype, but this did not reach statistical significance.. Serum and fecal biomarker concentrations are associated with endoscopic but not clinical disease activity in patients with Crohn's disease. Stimulated hsCRP concentration is affected significantly by select genetic polymorphisms.

Topics: Adult; Biomarkers; C-Reactive Protein; Colon; Colonoscopy; Crohn Disease; Feces; Female; Gene Frequency; Heterozygote; Homozygote; Humans; Interleukin-6; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Polymorphism, Genetic; Serum; Severity of Illness Index; Statistics as Topic

Biomarkers hold promise for identifying high-risk individuals who may go on to develop IBD as well as prognosticate disease behavior. Stool markers have not been readily accepted but may be more sensitive and specific than our serum biomarkers for evaluating disease activity. Ultimately, genomic and proteomic approaches will be used to identify novel biomarkers in IBD.

Topics: Biomarkers; C-Reactive Protein; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Disease Progression; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Prognosis; Risk Assessment

Correlation of endoscopic Crohn's disease activity with fecal calprotectin and lactoferrin is insufficiently studied. We evaluated the clinical significance of these neutrofil-derived proteins in assessment of Crohn's disease activity by comparing them with endoscopic disease activity and with Crohn's disease activity index (CDAI) and serum CRP.. A total of 77 CD patients underwent one or more ileocolonoscopies (n = 106) with scoring of Crohn's disease index of severity (CDEIS). Patients provided stool samples for calprotectin and lactoferrin measurements and blood samples for CRP. Clinical activity was based on the CDAI.. Both fecal calprotectin and lactoferrin correlated significantly with CDEIS (Spearman's r 0.729 and 0.773, P < 0.001). With a cutoff level of 200 microg/g for a raised fecal calprotectin concentration, sensitivity was 70%, specificity 92%, positive predictive value (PPV) 94%, and negative predictive value (NPV) 61% in predicting endoscopically active disease (CDEIS >/= 3). A fecal lactoferrin concentration of 10 microg/g as the cutoff value gave a sensitivity, specificity, PPV, and NPV of 66%, 92%, 94%, and 59%. Sensitivity of CDAI >/= 150 to detect endoscopically active disease was only 27%, specificity 94%, PPV 91%, and NPV 40%. A raised serum CRP (> 5 mg/l) gave a sensitivity, specificity, PPV, and NPV of 48%, 91%, 91%, and 48%.. For evaluation of Crohn's disease activity, based on endoscopic findings, more sensitive surrogate markers than is CDAI or CRP are fecal calprotectin and lactoferrin. These prove to be useful tools for estimation of disease activity in Crohn's disease.

Topics: Adult; Aged; Blood Chemical Analysis; C-Reactive Protein; Crohn Disease; Endoscopy, Gastrointestinal; Feces; Female; Humans; Intestines; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Severity of Illness Index

To assess cost-effectiveness of fecal lactoferrin (FL) as the initial diagnostic approach to symptomatic patients with ileal pouch-anal anastomosis (IPAA).. Four competing strategies [empiric metronidazole therapy (txMTZ), initial pouch endoscopy with biopsy (testBiop), initial FL assay followed by metronidazole therapy (testFL+MTZ), and initial FL assay followed by pouch endoscopy and biopsy (testFL+Biop)] were modeled in a decision tree.. In the base-case, the average cost per patient was $241 for testFL+MTZ, $251 for txMTZ, $405 for testFL+Biop, and $431 for testBiop. The testBiop strategy had greater effectiveness compared with txMTZ but at an incremental cost of $158 per day. The txMTZ strategy was slightly more costly and minimally more effective than testFL+MTZ with an incremental cost effectiveness of just over $12 per day. However, the testFL+MTZ strategy was associated with a 31% absolute reduction in antibiotic exposure compared with the txMTZ strategy.. Compared with empiric metronidazole therapy, FL before treatment with metronidazole is less costly with less exposure to antibiotics and less need for endoscopy, with only marginal decrease in effectiveness.

Topics: Anal Canal; Anastomosis, Surgical; Anti-Infective Agents; Biopsy; Colonic Pouches; Cost-Benefit Analysis; Crohn Disease; Decision Trees; Endoscopy; Feces; Humans; Ileum; Lactoferrin; Metronidazole; Pouchitis

Fecal calprotectin and lactoferrin are promising noninvasive biomarkers for intestinal inflammation. In Crohn's disease (CD), during anti-TNF-alpha (TNF-alpha) treatment, the clinical significance of these markers has, however, been insufficiently explored.. Among CD patients receiving anti-TNF-alpha therapy we assessed the role of fecal calprotectin and lactoferrin as surrogate markers for mucosal healing. Before and 3 months after the beginning of anti-TNF-alpha induction, 15 patients underwent ileocolonoscopy with scoring of the Crohn's Disease Index of Severity (CDEIS). Fecal samples for calprotectin and for lactoferrin measurements were collected and the Crohn's Disease Activity Index (CDAI) was calculated at the time of the endoscopies and 2 and 8 weeks after the first treatment.. The median CDEIS fell from 13.0 to 4.8 (P = 0.002) and CDAI from 158 to 68 (P = 0.005). Accordingly, the median fecal calprotectin concentration fell from 1173 microg/g to 130 microg/g (P = 0.001) and fecal lactoferrin from 105.0 microg/g to 2.7 microg/g (P = 0.001). Of the 15 patients, 11 (73%) showed an endoscopic response to treatment and 5 of these achieved endoscopic remission (CDEIS < 3). In those 5 patients the fecal calprotectin concentration declined from 1891 mug/g (range 813-2434) to 27 microg/g (13-130) and lactoferrin from 92.4 microg/g (35.5-235.6) to 1.9 microg/g (0.0-2.1).. Compared to pretreatment values, concentrations of fecal calprotectin and lactoferrin after the anti-TNF-alpha treatment were significantly lower. During anti-TNF-alpha therapy these fecal neutrophil-derived proteins may thus be useful surrogate markers for mucosal healing.

Topics: Adult; Biomarkers; Crohn Disease; Endoscopy, Gastrointestinal; Feces; Female; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Tumor Necrosis Factor-alpha; Young Adult

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

This study was designed to assess the role of fecal lactoferrin and calprotectin as markers of intestinal inflammation in patients with Crohn's disease who have undergone ileocolonic resection.. Sixty-three patients who had undergone ileocolonic resection for Crohn's disease with a median follow-up of 40.5 (range, 5-102) months were enrolled. Clinical examination and blood test were performed, and fecal lactoferrin and calprotectin levels were dosed. The predictors for fecal lactoferrin and calprotectin levels that resulted to be significant at the univariate analyses were included in two multiple regression analysis models.. The mean lactoferrin level was 21 +/- 3.9 microg/g and the mean calprotectin fecal level was 247 +/- 22.7 ng/ml. C-reactive protein levels (P < 0.01), calprotectin levels (P < 0.01), and the presence of clinical recurrence (P = 0.04) resulted to be independent predictors of lactoferrin levels. Only lactoferrin levels resulted to be an independent predictor for calprotectin fecal levels (P < 0.01).. Crohn's disease patients maintain high fecal levels of lactoferrin and calprotectin at long-term follow-up after resection of the diseased bowel even in case of clinical remission. The significant correlation between the two fecal markers may be the expression of the ongoing intestinal inflammation. Only lactoferrin significantly correlated with C-reactive protein and showed a reliable threshold value for systemic inflammation. Lactoferrin fecal levels may be a reliable indicator for intestinal inflammation influencing the systemic inflammatory status. The third predictor of lactoferrin fecal level was the presence of episodes of clinical recurrence during the postoperative follow-up.

Topics: Adolescent; Adult; Aged; Biomarkers; C-Reactive Protein; Colon; Crohn Disease; Cross-Sectional Studies; Feces; Female; Follow-Up Studies; Humans; Ileum; Iron; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Recurrence; Regression Analysis; Sensitivity and Specificity; Serum Albumin

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

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

The aims of this study were: 1) to examine whether the fecal levels of eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease (IBD); and 2) to examine the extracellular release of these proteins from eosinophils and their stability in feces by an in vitro study.. We investigated 42 patients with ulcerative colitis (UC), 37 patients with Crohn's disease (CD), and 29 control subjects. The stool samples were collected at 4 degrees C over 48 h and were homogenized. The fecal levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured by radioimmunoassay. Fecal Hb (Hb), alpha1-antitrypsin (AT), and lactoferrin (Lf) were also measured by ELISA.. Fecal ECP and EPX concentrations were significantly increased in both active UC and active CD compared to inactive UC and inactive CD, respectively. Fecal EPX concentration correlated with the fecal Hb, AT, and Lf concentrations more closely than fecal ECP concentration. Even in the inactive stage, CD patients who relapsed within the following 3 months showed higher fecal ECP and EPX concentrations compared to the patients who did not. EPX was released extracellularly more efficiently than ECP (18.6% vs 6.3%, after incubation for 15 min at 25 degrees C). EPX was more stable in the feces than ECP.. The measurement of eosinophil granule-derived proteins in feces is useful for evaluating disease activity and predicting relapse in patients with IBD. EPX may be more suitable than ECP as a fecal eosinophil marker.

Topics: Adult; alpha 1-Antitrypsin; Blood Proteins; Colitis, Ulcerative; Crohn Disease; Disease Progression; Eosinophil Granule Proteins; Eosinophil-Derived Neurotoxin; Eosinophils; Feces; Female; Hemoglobinometry; Humans; Inflammation Mediators; Lactoferrin; Male; Middle Aged; Radioimmunoassay; Ribonucleases

The utility of tests for fecal neutrophils in the setting of chronic diarrhea has not been established. The purpose of this study was to determine the causes of chronic diarrhea associated with fecal neutrophils.. One fecal specimen from each of 10 normal subjects, 26 patients with known microscopic colitis, 13 with celiac sprue, eight with Crohn's disease, four with ulcerative colitis, and 103 with chronic diarrhea of unknown origin, as well as 10 fecal specimens from a patient with chronic nongranulomatous enterocolitis were analyzed blindly for the presence of a neutrophil granule protein called lactoferrin using a commercial latex agglutination kit. Diagnostic evaluation of the 103 patients with chronic diarrhea was carried out to determine the diagnostic accuracy of this test for chronic inflammatory bowel disease.. None of the normal control subjects, three of 39 patients with microscopic colitis or celiac sprue, all 10 specimens from the patient with enterocolitis, and all 12 control patients with ulcerative colitis or Crohn's disease had a positive fecal lactoferrin test. Eleven of 103 patients with chronic diarrhea presenting without a diagnosis had a positive test, and all were diagnosed with an inflammatory condition of the colon (five-, ulcerative colitis; four-, Crohn's disease; one-, ischemic colitis; and one-, microscopic colitis). Only one patient with inflammatory bowel disease had a negative lactoferrin test. The sensitivity, specificity, and positive and negative predictive values of the fecal lactoferrin test for ulcerative or Crohn's colitis were 90%, 98%, 82%, and 99%, respectively.. The major cause of fecal neutrophils in patients with chronic diarrhea is chronic inflammatory bowel disease of the colon. The latex agglutination test for fecal lactoferrin offers a highly sensitive, specific, and simple means for detection of fecal neutrophils in these patients.

Topics: Celiac Disease; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Diarrhea; Feces; Female; Humans; Lactoferrin; Latex Fixation Tests; Male; Neutrophils; Occult Blood; Sensitivity and Specificity

1. One hypothesis for the link between inflammatory bowel disease and primary sclerosing cholangitis is that neutrophil activators, such as bacterial chemotactic peptides or neutrophil granule products themselves, pass from the inflamed colon to the liver via an enterohepatic circulation. However, there are no data on biliary concentrations of neutrophil granule products in patients with active and inactive inflammatory bowel disease.2. Gall bladder bile was obtained at laparotomy from 42 patients with ulcerative colitis and 21 patients with Crohn's disease. Biliary lactoferrin and myeloperoxidase concentrations were quantified by ELISA.3. In active ulcerative colitis, the mean lactoferrin concentration in gall bladder bile of 2.8+/-0.40 mg/l was higher than that seen after colectomy (1.2+/-0.11 mg/l; P<0.0001) or in patients with pouchitis (1.8+/-0.34 mg/l; P=0.06). In active Crohn's colitis, the mean lactoferrin concentration was 3.7+/-0.9 mg/l, compared with 1.1+/-0. 24 mg/l in the post-colectomy group (P<0.05) and 3.1+/-0.71 mg/l in those with active ileitis or ileocolitis. In contrast, biliary myeloperoxidase concentrations were low and comparable in all groups, with a mean concentration in the 42 patients with ulcerative colitis of 11.2+/-1.9 microgram/l.4. In contrast to myeloperoxidase, biliary lactoferrin concentrations are increased in active ulcerative colitis and Crohn's disease, and fall with colectomy and with disease remission. These findings indirectly support the hypothesis that bacterial chemotactic peptides (which induce selective degranulation of neutrophil secondary granules), and/or lactoferrin itself, undergo an enterohepatic circulation.

Topics: Acute Disease; Adolescent; Adult; Aged; Bile; Bile Acids and Salts; Cholangitis, Sclerosing; Chromatography, Gel; Colectomy; Colitis, Ulcerative; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Female; Gallbladder; Humans; Lactoferrin; Male; Middle Aged; Peroxidase; Pouchitis; Statistics, Nonparametric

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

Bactericidal/permeability-increasing protein (BPI), a constituent of primary neutrophil granules, is a potent natural antibiotic and an antineutrophil cytoplasm antibody (ANCA) antigen in cases of vasculitis in which the target antigen is neither myeloperoxidase (MPO) nor proteinase-3 (PR3).. To investigate BPI as a possible target antigen for ANCAs in inflammatory bowel disease.. ANCAs were detected by routine immunofluorescence (IIF) and solid phase enzyme linked immunosorbent assay (ELISA) performed for antibodies to the purified neutrophil granule proteins; MPO, PR3, cathepsin-G, lactoferrin, and BPI in serum samples from 88 patients with inflammatory bowel disease (36 with Crohn's disease, 52 with ulcerative colitis). Thirty patients with bacterial enteritis acted as controls.. Significantly more patients with ulcerative colitis were ANCA positive by IIF (60%) than patients with Crohn's disease (28%) or infectious enteritis (23%) (p < 0.001). IgG anti-BPI antibodies were present in 29% of patients with ulcerative colitis, 14% of patients with Crohn's disease, and 23% of patients with infectious enteritis, occurring in 44% of those patients with inflammatory bowel disease who were ANCA positive by IIF. Antibodies to other ANCA antigens were rare. The presence of ANCAs was not related to either disease activity or extent; presence of anti-BPI antibodies was significantly related to both a lower serum albumin concentration (p = 0.001) and a higher erythrocyte sedimentation rate (p = 0.02) in patients with ulcerative colitis, and to colonic involvement in patients with Crohn's disease (p = 0.01).. BPI is a significant minority target antigen for ANCAs in inflammatory bowel disease that seems related to colonic Crohn's disease and disease activity in ulcerative colitis. Anti-BPI antibodies occur in infectious enteritis.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Antimicrobial Cationic Peptides; Blood Proteins; Case-Control Studies; Cathepsin G; Cathepsins; Colitis, Ulcerative; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin G; Lactoferrin; Male; Membrane Proteins; Middle Aged; Peroxidase; Prospective Studies; Serine Endopeptidases

Immunisation against the mycobacterial heat shock protein (hsp-65) has been proposed to lead to production of autoantibodies against human lactoferrin. Such antibodies occur in ulcerative colitis and in primary sclerosing cholangitis. This study analysed the distribution of hsp-65 and lactoferrin in biopsy specimens from patients with inflammatory bowel disease and primary sclerosing cholangitis and studied whether immunisation against mycobacterial hsp-65 resulted in production of antilactoferrin antibodies and vice versa. Polyclonal rabbit antihuman lactoferrin and monoclonal mouse anti-hsp-65 (ML30) were used for immunohistochemistry on biopsy specimens from patients with inflammatory bowel disease and primary sclerosing cholangitis. Rats were immunised against human lactoferrin and mycobacterial hsp-65 respectively. Antibody measurements were done by enzyme immunosorbent assays. It was found that lactoferrin and hsp-60/65 were not codistributed. Lactoferrin was found on vascular endothelium and in nonparenchymal liver cells both in inflamed and uninflamed tissues, but only in the hepatocytes of inflamed liver. ML30 reactivity was not inhibited by antilactoferrin antibodies. Rat anti-hsp-65 serum had no detectable antilactoferrin antibodies. In conclusion, antilactoferrin antibodies probably do not arise by immunisation against mycobacterial hsp-65. Both nonparenchymal cells and hepatocytes probably participate in clearance of lactoferrin. Endothelial exposure of lactoferrin may have pathogenic implications in diseases with antilactoferrin autoantibodies.

Topics: Animals; Antibodies; Bacterial Proteins; Chaperonin 60; Chaperonins; Cholangitis, Sclerosing; Colitis, Ulcerative; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Lactoferrin; Rabbits; Rats; Rats, Inbred Lew

1) To investigate which neutrophil-derived proteins in feces most accurately reflect disease activity in inflammatory bowel disease. 2) To examine the extracellular release of these proteins by activated neutrophils and their stability in feces by in vitro study.. We studied 41 patients (91 samples) with ulcerative colitis (UC), 34 patients (105 samples) with Crohn's disease (CD), and 25 control subjects. Fecal levels of lactoferrin (Lf), polymorphonuclear neutrophil elastase (PMN-E), myeloperoxidase (MPO), and lysozyme (Lys) were measured by ELISA. We also measured fecal hemoglobin (Hb) and alpha 1-antitrypsin (alpha 1-AT), useful markers of disease activity in UC and CD, respectively. For the in vitro study, blood samples were stimulated with phorbol myristate acetate or latex beads. For the assessment of stability, homogenized stool samples were stored at 4 degrees C, 25 degrees C, and 37 degrees C for various periods.. 1) Fecal Lf, PMN-E, MPO, and Lys concentrations were significantly increased in the active phase of the disease compared to the inactive phase in both UC and CD. 2) Fecal Lf, PMN-E, MPO, and Lys concentrations correlated significantly with fecal Hb concentration in UC, whereas fecal Lf, PMN-E, and MPO concentrations correlated significantly with alpha 1-AT concentration in CD. In UC, fecal Lf, PMN-E, MPO, and Lys concentrations were high in 15, 9, 14, and 14 samples, respectively, of 25 samples with normal Hb concentration. In CD, fecal Lf, PMN-E, and MPO concentrations were high in 19, 10, and 16 samples, respectively, of 30 samples with normal alpha 1-AT concentration. 3) The extracellular release of Lf was the most efficient and this molecule was the most stable in feces.. Both our clinical and our in vitro studies suggested that Lf is the most suitable of these proteins to use as neutrophil-derived fecal marker of inflammation for clinical application.

Topics: Adult; alpha 1-Antitrypsin; Biomarkers; Colitis, Ulcerative; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Feces; Hemoglobins; Humans; Lactoferrin; Leukocyte Elastase; Middle Aged; Muramidase; Neutrophils; Pancreatic Elastase; Peroxidase; Proteins

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

We have developed a new immunochemical test for fecal lactoferrin (LF) utilizing an enzyme-linked immunosorbent assay (ELISA). The ELISA had a sensitivity of about 10 micrograms/L of lactoferrin and the measurable range was 10.0-1000.0 micrograms/L (1.0-100.0 micrograms LF/g feces). The stability of lactoferrin in feces was greater than that of myeloperoxidase and leucocyte elastase. The fecal concentration of lactoferrin (mean +/- SD) in 35 normal subjects was 0.75 +/- 0.83 microgram/g feces, whereas that in 24 patients with colon cancer was 74.4 +/- 88.3 micrograms/g feces. The fecal lactoferrin concentration of 38 patient with active ulcerative colitis was 307.4 +/- 233.9 micrograms/g feces, and that in 36 patients with active Crohn's disease was 191.7 +/- 231.1 micrograms/g feces. The ELISA for human fecal lactoferrin might be useful in the diagnosis of colon disease.

Topics: Adolescent; Adult; Aged; Colitis, Ulcerative; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Feces; Female; Humans; Lactoferrin; Male; Middle Aged; Regression Analysis

The aim was to study the level of salivary proteins with antimicrobial properties in persons with Crohn's disease. Twenty-five patients were recruited, 13 with ongoing symptoms (acute group) and 12 free of clinical signs of the disease at the time of the investigation (nonacute group). A control group matched to the nonacute group was also included in the study. Unstimulated and stimulated whole saliva samples were collected, and the secretion rates estimated. Unstimulated saliva was analyzed for concentrations of total protein, peroxidase, thiocyanate, slgA, lactoferrin, lysozyme, and for specific bacteria aggregation ability. Numbers of mutans streptococci and lactobacilli in saliva were determined, and dental caries status was examined. No differences were found among the groups regarding salivary flow rate, total protein, or any of the antimicrobial proteins. However, three patients with Crohn's disease had no detectable slgA in saliva compared with none in the control group. The lactobacillus count and the number of decayed tooth surfaces were higher in the nonacute group than in the control group.

Topics: Adult; Aged; Case-Control Studies; Colony Count, Microbial; Crohn Disease; Dental Caries; Dental Caries Susceptibility; DMF Index; Female; Humans; Immunity, Innate; Immunoglobulin A, Secretory; Lactobacillus; Lactoferrin; Male; Middle Aged; Muramidase; Peroxidases; Prevalence; Risk Factors; Saliva; Salivary Proteins and Peptides; Salivation; Secretory Rate; Streptococcus mutans

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

Fifty two serum samples from patients with Crohn's disease, 24 from patients with ulcerative colitis, and 12 from patients with primary sclerosing cholangitis were analysed for the presence of anti-neutrophil cytoplasm antibodies (ANCA) of IgG and IgA class by means of enzyme linked immunosorbent assays using lactoferrin, myeloperoxidase, and antigen extracted from azurophil granules, 'alpha antigen' (that is, an antigen preparation containing proteinase 3) as substrates. A high frequency of positive tests for IgG anti-lactoferrin antibodies was found in sera from patients with ulcerative colitis (50%) and primary sclerosing cholangitis (50%). In Crohn's disease only 4 of 52 (8%) sera had anti-lactoferrin antibodies--in all four instances the sera belonged to patients with disease involving the colon. All patients with sclerosing cholangitis and positive tests for anti-lactoferrin had ulcerative colitis. Low levels of IgG antibodies against myeloperoxidase or alpha antigen were also found occasionally in sera from patients with ulcerative colitis and primary sclerosing cholangitis. IgA antibodies directed against lactoferrin and alpha antigen (but not myeloperoxidase) were seen in all three conditions.

Topics: Adult; Aged; Autoantibodies; Blotting, Western; Cholangitis, Sclerosing; Colitis, Ulcerative; Crohn Disease; Cytoplasm; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin A; Immunoglobulin G; Lactoferrin; Male; Microscopy, Fluorescence; Middle Aged; Neutrophils

Autoantibodies directed against polymorphonuclear neutrophils (PMN) have been observed in serum from patients with ulcerative colitis (UC), Crohn's disease (CD) and primary sclerosing cholangitis (PSC) using indirect immunofluorescence and fixed granulocyte ELISA. Our study demonstrates the presence in the serum of these patients of autoantibodies which bind to an azurophilic granule component distinct from proteinase 3, elastase and myeloperoxidase. These autoantibodies thus belong to the ANCA family, but their antigen specificity differs from the already characterized ANCA antigens. We have found that the same ANCA antigen target, named UC-antigen, was recognized by serum IgG from patients with UC, CD and PSC. It was purified by Matrex Gel Orange A dye affinity chromatography and subsequent immunoabsorption of contaminant proteinase 3 with immobilized anti-proteinase 3 MoAb. The identity between this UC antigen and cathepsin G was demonstrated by their coelution from Matrex Gel Orange A column and the parallel titration of cathepsin G-specific enzymatic activity and UC-ANCA binding, both in partially purified UC antigen and in highly pure cathepsin G. Furthermore, the use of cathepsin G ELISA confirmed that UC, CD and PSC patients' IgG did indeed bind to cathepsin G. Comparison of the results obtained with azurophilic granule- and cathepsin G-ELISA as well as inhibition of ANCA binding by anti-cathepsin G polyclonal antibodies, revealed that in some patients cathepsin G is the main azurophilic granule target of ANCA while others have other ANCA specificities. The fact that UC, CD and PSC are frequently associated with cathepsin G ANCA, while rarely occurring in other types of vasculitis, is intriguing but suggests that these diseases may have a common pathogenetic mechanism.

Topics: Autoantibodies; Cathepsin G; Cathepsins; Cholangitis, Sclerosing; Colitis, Ulcerative; Crohn Disease; Cytoplasmic Granules; Humans; Lactoferrin; Myeloblastin; Neutrophils; Pancreatic Elastase; Peroxidase; Serine Endopeptidases