gastrins and Autoimmune-Diseases

Autoimmune diseases, characterized by an alteration of the immune system which results in a loss of tolerance to self antigens often coexist in the same patient. Autoimmune atrophic gastritis, characterized by the development of antibodies agains parietal cells and against intrinsic factor, leads to mucosal destruction that affects primarily the corpus and fundus of the stomach. Autoimmune atrophic gastritis is frequently found in association with thyroid disease, including Hashimoto's thyroiditis, and with type 1 diabetes mellitus, Other autoimmune conditions that have been described in association with autoimmune atrophic gastritis are Addison's disease, chronic spontaneous urticaria, myasthenia gravis, vitiligo, and perioral cutaneous autoimmune conditions, especially erosive oral lichen planus. Interestingly, however, celiac disease, another frequent autoimmune condition, seems to play a protective role for autoimmune atrophic gastritis. The elevated prevalence of autoimmune disease clustering should prompt the clinicial to exclude concomitant autoimmune conditions upon diagnosis of any autoimmune disease.

Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Biomarkers; Comorbidity; Disease Susceptibility; Gastrins; Gastritis, Atrophic; Humans; Intrinsic Factor; Parietal Cells, Gastric; Pepsinogens; Prevalence; Sensitivity and Specificity

Gastrin has been identified as the principal effector of gastric secretion, but several studies have demonstrated its role as a biomarker of cancer risk and as a growth factor for colorectal, stomach, liver, and pancreatic cancer. Hypergastrinemia characterizes autoimmune gastritis, with body and fundic gland atrophy and increased risk for both gastric adenocarcinoma and neuroendocrine tumors. Gastric type I carcinoids develop in the context of autoimmune gastritis because of the stimulus exerted by gastrin on enterochromaffin-like cells and remain gastrin-sensitive for long durations because the removal of hypergastrinemia leads to tumor regression. The treatment of gastric carcinoid is still open to debate, but when the disease frequently relapses, or is multicentric or infiltrating, surgery is advocated or, in the alternative, a costly and long-lasting treatment with long-acting somatostatin analogues is prescribed. A technology allowing the preparation of an immunogen eliciting an immune system response with generation of antibodies against G17 has been developed. This vaccine has been tested in patients with colorectal, pancreatic or advanced gastric cancer. The vaccine has also been used in the treatment of gastric type I carcinoids, and the administration of G17DT in patients harboring these lesions leads to carcinoid regression. Antigastrin vaccination in the treatment of gastrointestinal cancer obviously needs validation, but this immunotherapy may well represent a simple, inexpensive, and active 'adjuvant' treatment.

Topics: Adenocarcinoma; Autoimmune Diseases; Cancer Vaccines; Carcinoid Tumor; Colorectal Neoplasms; Gastrins; Gastritis; Humans; Liver Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms

The most frequent conditions of hypergastrinemia in man are the Zollinger-Ellison syndrome with autonomous gastrin hypersecretion by the tumour cell and reactive hypergastrinemia in type A autoimmune chronic atrophic gastritis with achlorhydria causing unrestrained gastrin release from the gastrin-producing antral G-cells. Both entities differ with respect to the pH in the gastric fluid, which is < 2 in patients with Zollinger-Ellison syndrome and neutral in type A gastritis. Other conditions with moderate hypergastrinemia as treatment with proton pump inhibitors, gastric outlet obstruction, previous vagotomy, chronic renal failure or short bowel syndrome are of minor clinical importance.

Topics: Autoimmune Diseases; Carcinoid Tumor; Diagnosis, Differential; Duodenal Neoplasms; Enterochromaffin-like Cells; Gastric Mucosa; Gastrinoma; Gastrins; Gastritis, Atrophic; Humans; Hyperplasia; Pancreatic Neoplasms; Stomach Neoplasms; Zollinger-Ellison Syndrome

The role of gastrin in the pathophysiology of two diseases affecting the human stomach, the Zollinger Ellison syndrome (ZES) and the pernicious anemia (PA), is reviewed. Both diseases present chronic hypergastrinemia but from different origins. The ZES is characterized by the occurrence of ectopic endocrine gastrin-secreting tumors and PA by a fundic atrophic gastritis leading to complete atrophy of fundus and resulting in achlorhydria. In PA, the lack of acid induces continuous gastrin cell activation and is responsible for the subsequent gastrin hypersynthesis and secretion. In ZES, hypergastrinemia causes hypertrophy of the oxyntic mucosa, which, in addition, displays hyperplasia of parietal and mucus cells. In both diseases, hypergastrinemia also induces the hyperproliferation of enterochromaffin-like endocrine cells in the fundic mucosa, which can offer all aspects from hyperplasia, then dysplasia, until true carcinoid tumor. The influence of antisecretory treatments and MEN 1 in the ZES as well as that of several other factors and antrectomy in PA on the behavior of the different gastric cells is evoked. Finally, the role that gastrin and its receptor play in the maintenance of the normal development of gastric mucosa and gastric acid secretion is emphasized by results observed in gene knockout models.

Topics: Anemia, Pernicious; Animals; Atrophy; Autoimmune Diseases; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Hypertrophy; Mice; Mice, Knockout; Multiple Endocrine Neoplasia Type 1; Zollinger-Ellison Syndrome

Three cases of gastric carcinoid polypi associated to atrophic gastritis and high levels of seric gastrin, are presented. One of the cases was a multiple micropolyposis the literature regarding this association is reviewed and the therapy discussed. Tumors of greater than 2 cm have to be considered potentially malignant and be treated likewise. The treatment of the micropolyposis is not well established.

Topics: Achlorhydria; Adult; Autoimmune Diseases; Carcinoid Tumor; Female; Follow-Up Studies; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Polyps; Pyloric Antrum; Stomach Neoplasms

Topics: Adrenal Cortex Hormones; Anemia, Pernicious; Animals; Antigen-Antibody Complex; Antigens; Autoantibodies; Autoimmune Diseases; Chronic Disease; Dogs; Female; Gastric Mucosa; Gastrins; Gastritis; Guinea Pigs; Haplorhini; Humans; Immunity, Cellular; Intrinsic Factor; Male; Rabbits; Rats; Vitamin B 12 Deficiency

Topics: Adrenal Cortex Hormones; Adult; Anemia, Pernicious; Atrophy; Autoantibodies; Autoimmune Diseases; Binding Sites, Antibody; Child; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Immunity, Cellular; Immunoglobulin A; Immunoglobulin G; Intrinsic Factor; Vitamin B 12

Topics: Adolescent; Adult; Aged; Anemia, Hypochromic; Anemia, Pernicious; Atrophy; Autoantibodies; Autoimmune Diseases; Chronic Disease; Female; Gastrins; Gastritis; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Postgastrectomy Syndromes; Stomach Neoplasms; Stomach Ulcer

Topics: Anemia, Pernicious; Antibodies; Atrophy; Autoimmune Diseases; Capillaries; Chronic Disease; Dyspepsia; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Hypertrophy; Intrinsic Factor; Metaplasia; Mitosis; Pentagastrin; Pepsin A; Peptic Ulcer; Pyloric Antrum; Radiography; Stomach; Stomach Neoplasms; Thyroid Diseases; Vagotomy

Topics: Autoantibodies; Autoimmune Diseases; Cholecystokinin; Diabetes Mellitus; Gastrins; Gastrointestinal Hormones; Glucagon; Glucose; Humans; Insulin; Secretin; Trace Elements

Netazepide, a gastrin/cholecystokinin 2 receptor antagonist, once daily for 12 weeks reduced the number of tumours and size of the largest one in 16 patients with autoimmune chronic atrophic gastritis (CAG), achlorhydria, hypergastrinaemia and multiple gastric neuroendocrine tumours (type 1 gastric NETs), and normalized circulating chromogranin A (CgA) produced by enterochromaffin-like cells, the source of the tumours. The aim was to assess whether longer-term netazepide treatment can eradicate type 1 gastric NETs.. After a mean 14 months off netazepide, 13 of the 16 patients took it for another 52 weeks. Assessments were: gastroscopy; gene-transcript expression in corpus biopsies using quantitative polymerase chain reaction; blood CgA and gastrin concentrations; and safety assessments.. While off-treatment, the number of tumours, the size of the largest one, and CgA all increased again. Netazepide for 52 weeks: cleared all tumours in 5 patients; cleared all but one tumour in one patient; reduced the number of tumours and size of the largest one in the other patients; normalized CgA in all patients; and reduced mRNA abundances of CgA and histidine decarboxylase in biopsies. Gastrin did not increase further, confirming that the patients had achlorhydria. Netazepide was safe and well tolerated.. A gastrin/cholecystokinin 2 receptor antagonist is a potential medical and targeted treatment for type 1 gastric NETs, and an alternative to regular gastroscopy or surgery. Treatment should be continuous because the tumours will regrow if it is stopped. Progress can be monitored by CgA in blood or biomarkers in mucosal biopsies.

Topics: Achlorhydria; Aged; Autoimmune Diseases; Benzodiazepinones; Chromogranin A; Gastrins; Gastritis, Atrophic; Histidine Decarboxylase; Humans; Middle Aged; Neuroendocrine Tumors; Phenylurea Compounds

To explore the prevalence of autoimmune gastritis in chronic hepatitis C virus (HCV) patients and the influence of alpha-interferon (IFN) treatment on autoimmune gastritis.. We performed a prospective study on 189 patients with positive anti-HCV and viral RNA enrolled in a 12-month IFN protocol. We evaluated: a) the baseline prevalence of autoimmune gastritis, b) the impact of IFN treatment on development of biochemical signs of autoimmune gastritis (at 3, 6 and 12 months), c) the evolution after IFN withdrawal (12 months) in terms of anti-gastric-parietal-cell antibodies (APCA), gastrin, anti-thyroid, and anti-non-organ-specific antibodies.. APCA positivity and 3-fold gastrin levels were detected in 3 (1.6 %) and 9 (5 %) patients, respectively, at baseline, in 25 (13 %) and 31 (16 %) patients at the end of treatment (both P<0.001, vs baseline), and in 7 (4 %) and 14 (7 %) patients 12 months after withdrawal (P=0.002 and P=0.01 respectively, vs baseline; P=not significant vs end of treatment). The development of autoimmune gastritis was strictly associated with the presence of autoimmune thyroiditis (P =0.0001), no relationship was found with other markers of autoimmunity.. In HCV patients, IFN frequently precipitates latent autoimmune gastritis, particularly in females. Following our 12-month protocol, the phenomenon generally regressed. Since APCA positivity and high gastrin levels are associated with the presence of antithyroid antibodies, development of autoimmune thyroiditis during IFN treatment may provide a surrogate preliminary indicator of possible autoimmune gastritis to limit the need for invasive examinations.

Topics: Adult; Aged; Antiviral Agents; Autoimmune Diseases; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Hepatitis C, Chronic; Humans; Interferon-alpha; Male; Middle Aged; Organ Specificity; Parietal Cells, Gastric; Prevalence; Prospective Studies; Thyroid Gland; Treatment Outcome

Gastric polyps represent an abnormal proliferation of the gastric mucosa. Chronic atrophic autoimmune gastritis (CAAG) targets parietal cells and results in hypo-achlorhydria and hypergastrinemia, which exerts a proliferative effect on the gastric mucosa.. We investigate the incidence of gastric polyps in CAAG patients.. This is a single-center retrospective study examining patients with confirmed CAAG from January 1990 until June 2022. Demographic, clinical, biochemical, and serological data were collected for each included patient. The histopathological characteristics of the detected polyps were recorded.. A total of 176 CAAG patients were included. Eighty-nine (50.5%) had 163 incidental polyps. Seventy-six patients (85%) had 130 non-endocrine lesions, among which 118 (90.7%) were inflammatory, 6 (4.6%) adenomatous, and 4 (3%) fundic; 33 patients (37%) had gastric neuroendocrine neoplasms (gNENs), and 21 (23.6%) both; one had MALToma and one gastric adenocarcinoma. Higher circulating levels of gastrin and chromogranin A were observed among patients with polyps (median 668 vs 893 pg/ml p = 0.0237, 146 vs 207 ng/ml p = 0.0027, respectively).. CAAG implies a high incidence of gNENs and exocrine lesions. Gastrin plays a possible trophic role on the mucosa. Further evidence is needed to validate its predictive role for increased polyp risk in CAAG.

Topics: Autoimmune Diseases; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Atrophic; Humans; Polyps; Precancerous Conditions; Retrospective Studies; Stomach Neoplasms

Simple objective modalities are required for evaluating suspected autoimmune gastritis (AIG). This cross-sectional study aimed to examine whether pepsinogen, gastrin, and endoscopic findings can predict AIG. The diagnostic performance of endoscopic findings and serology in distinguishing AIG was evaluated. AIG was diagnosed in patients (N = 31) with anti-parietal cell antibody and/or intrinsic factor antibody positivity and histological findings consistent with AIG. Non-AIG patients (N = 301) were seronegative for anti-parietal cell antibodies. Receiver operating characteristic curve analysis of the entire cohort (N = 332) identified an endoscopic atrophic grade cutoff point of O3 on the Kimura-Takemoto classification (area under the curve [AUC]: 0.909), while those of pepsinogen-I, I/II ratio, and gastrin were 20.1 ng/mL (AUC: 0.932), 1.8 (AUC: 0.913), and 355 pg/mL (AUC: 0.912), respectively. In severe atrophy cases (≥ O3, N = 58, AIG/control; 27/31), the cutoff values of pepsinogen-I, I/II ratio, and gastrin were 9.8 ng/mL (AUC: 0.895), 1.8 (AUC: 0.86), and 355 pg/mL (AUC: 0.897), respectively. In conclusion, endoscopic atrophy is a predictor of AIG. High serum gastrin and low pepsinogen-I and I/II ratio are predictors even in the case of severe atrophy, suggesting their usefulness when the diagnosis of AIG is difficult or as serological screening tests.

Topics: Atrophy; Autoantibodies; Autoimmune Diseases; Cross-Sectional Studies; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Pepsinogen A

The aims of the present study are to evaluate non-invasive screening tests for autoimmune gastritis (AIG) and re-evaluate histopathological classification.. We screened candidates of AIG in JCHO Shiga Hospital between May 2012 and January 2020. The screening criteria were as follows: endoscopic O-p atrophy with Updated Kimura-Takemoto classification, 3 + pepsinogen (PG) test, low serum vitamin B. Twenty-two of 28 (78.6%) patients who met the screening criteria were histopathologically confirmed as AIG. Common clinical findings in the AIG patients were 10 × or greater anti-PC antibody, elevated serum gastrin greater than 172 pg/mL and endoscopic atrophy O-1 or greater. The areas under the curve of PG I, PG II and PG I/II ratio were 0.81, 0.29 and 0.98, respectively. Among histopathologically confirmed AIG patients, 4 and 18 patients were histopathologically classified into florid and end stages, respectively, while no patients into early stage. We could not find a significant difference between florid and end stages in the screening items studied.. Florid and end stages in histopathological classification are both advanced-stage AIG in clinical aspects. Our screening criteria without biopsy are applicable to screen clinically-advanced AIG with 78.6% positive predictive value. PG I and PG I/II ratio may be useful to screen AIG. However, we may need other criteria to screen early stage of AIG.

Topics: Atrophy; Autoimmune Diseases; Gastrins; Gastritis; Humans; Japan; Pepsinogen A

Patients with autoimmune atrophic gastritis (AAG) often complain of acid reflux symptoms, despite the evidence of hypo-achlorhydria. Rome IV criteria are used to define functional esophageal disorders. Our aim was to characterize gastroesophageal reflux disease (GERD) phenotypes in patients with AAG.. Between 2017-2018, 172 AAG patients were evaluated at Gastro-Oncology outpatient clinic of University of Padua. Of them, 38 patients with reflux symptoms underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH). Seventy-six AAG consecutive patients asymptomatic for gastroesophageal reflux were selected as age and gender matched controls. Serum biomarkers (pepsinogens, gastrin-17 and Helicobacter pylori antibodies), upper endoscopy, histology and clinical data were compared.. Out of 38/172 (22%) AAG patients with reflux symptoms, 2/38 had a GERD diagnosis based on abnormal esophageal acid exposure and 6/38 had a major motility disorder (i.e. outflow obstruction). Among the 30/38 patients with normal endoscopic findings, 9/30 had reflux hypersensitivity, 19 functional heartburn, 1 functional globus, 1 functional chest pain according to the Rome IV criteria. Antral atrophy, advanced corpus atrophy and OLGA stage were more frequent in controls than in reflux patients (p=0.01, p=0.031, p=0.01, respectively). No differences were found for serum biomarkers and symptom presentation. Most of the patients received proton pump inhibitors (PPIs) treatment (87%), with a minority (34%) reporting clinical benefit.. Reflux symptoms are relatively common in AAG patients, but a firm diagnosis of GERD is rare (5%), whereas most of the patients have a functional disorder. PPI treatment is mostly clinical ineffective and should not be largely indicated.

Topics: Aged; Antibodies, Bacterial; Autoimmune Diseases; Biomarkers; Endoscopy, Digestive System; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter pylori; Humans; Italy; Male; Middle Aged; Pepsinogens; Prospective Studies; Proton Pump Inhibitors

Gastrin regulates gastric acid secretion, and gastrin secretion itself is regulated by the negative feedback system of gastric acidity. Autoimmune gastritis (AG) is a disease where parietal cells are destroyed, resulting in decreased acid production and an elevated serum gastrin level. We herein report 2 AG cases with marked hypergastrinemia (>5,000 pg/mL). In both cases, 24-hour gastric pH monitoring showed no time when gastric pH was <2, and immunohistochemistry revealed more than 140 gastrin-positive cells per linear millimeter at the antral mucosa. This is the first report to confirm the relationship between marked hypergastrinemia and G-cell hyperplasia with AG.

Topics: Aged; Autoimmune Diseases; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Hyperplasia; Immunohistochemistry

Autoimmune atrophic gastritis (AIG) is very rare in children. Despite a better understanding of histopathologic changes and serological markers in this disease, underlying etiopathogenic mechanisms and the effect of Helicobacter pylori (H pylori) infection are not well known. We aimed to investigate the relation between AIG and H pylori infection in children.. We evaluated the presence of AIG and H pylori infection in fifty-three patients with positive antiparietal cell antibody (APCA). Demographic data, clinical symptoms, laboratory and endoscopic findings, histopathology, and presence of H pylori were recorded.. The children were aged between 5 and 18 years, and 28 (52.8%) of them were male. Mean age was 14.7 ± 2.6 years (median: 15.3; min-max: 5.2-18), and 10 (18.8%) of them had AIG confirmed by histopathology. In the AIG group, the duration of vitamin B12 deficiency was longer (P = .022), hemoglobin levels were lower (P = .018), and APCA (P = .039) and gastrin (P = .002) levels were higher than those in the non-AIG group. Endoscopic findings were similar between the two groups. Intestinal metaplasia was higher (P = .018) in the AIG group. None of the patients in the AIG group had H pylori infection (P = .004). One patient in the AIG group had enterochromaffin-like cell hyperplasia.. Our results show that, in children, H pylori infection may not play a role in AIG. AIG could be associated with vitamin B12 deficiency, iron deficiency, and APCA positivity in children. APCA and gastrin levels should be investigated for the early diagnosis of AIG and intestinal metaplasia.

Topics: Adolescent; Anemia, Iron-Deficiency; Autoimmune Diseases; Child; Child, Preschool; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Parietal Cells, Gastric; Retrospective Studies; Stomach; Vitamin B 12 Deficiency

Autoimmune metaplastic atrophic gastritis (AMAG) is an underrecognized entity, especially in its early stage. This study assessed whether the use of gastrin immunohistochemistry would increase sensitivity for diagnosing early AMAG.. Three-hundred gastric biopsies were prospectively stained for gastrin by immunohistochemistry. Inclusion criteria included well-oriented gastric mucosa with mucus glands and minimal plasma cell infiltrate not suspected to represent pyloric metaplasia. Patient age, sex, designated location of biopsy, presence or absence of intestinal metaplasia, and clinical information were not criteria. Any case with absence of gastrin-positive endocrine cells reflexed to chromogranin immunohistochemistry. Maloriented biopsies or cases with current Helicobacter infection were excluded.. The 298-patient study cohort comprised 222 females (mean age, 47 years; range, 16-80 years) and 76 males (mean age, 49 years; range, 7-80 years). Biopsies were designated as "antral/antral nodules" (61%), and the rest were labeled "gastric/random stomach" (39%). Nine cases (3%) exhibited absence of gastrin-positive endocrine cells; one of those showed endocrine cell hyperplasia by chromogranin staining.. Pathologists should be aware of the histologic features of early AMAG and meticulously analyze tissue regardless of specimen labeling. Gastrin immunostain is a supplemental diagnostic tool when encountering inflamed antral-appearing specimens.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Biopsy; Child; Diagnosis, Differential; False Negative Reactions; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Immunohistochemistry; Male; Middle Aged; Prospective Studies; Pyloric Antrum; Young Adult

Chronic atrophic autoimmune gastritis (CAAG) can lead to the development of gastric neuroendocrine tumors (gNETs) and can be accompanied by other autoimmune diseases. This study aimed to determine, in CAAG patients, the association of gNET development, the prevalence of autoimmune diseases other than CAAG, the association of autoimmunity, and gNET development with pepsinogen I, II, gastrin-17, and Helicobacter pylori infection analysis.. We determined the prevalence of gNETs and other autoimmune diseases and analyzed pepsinogen I and II, gastrin-17 serum levels, and H. pylori infection in all patients diagnosed with CAAG at our hospital between 2013 and 2017.. A total of 156 patients were studied and in 15.4% was observed concomitant gNET. Approximately 68.6% had at least 1 other autoimmune disease at diagnosis of CAAG. Approximately 60.9% had autoimmune thyroiditis, followed by diabetes (19.9%) and autoimmune polyendocrine syndrome (12.8%). CAAG patients with and without gNET had similar rates of comorbidity with other autoimmune diseases, but the pepsinogen I/II ratio was lower in patients with gNET (1.6 vs 4.5, P = 0.018). Receiver operating characteristic curve analyses identified a pepsinogen I/II ratio <2.3 and gastrin-17 levels >29.6 pmol/L as cutoffs distinguishing CAAG patients with gNET from those without. The combined use of these cutoff correctly identified 16 of the 18 CAAG patients with gNET (P = 0.007). H. pylori infection was observed in 28.7% of cases tested but did not associate with gNET.. This study suggests that a low pepsinogen I/II ratio and high gastrin-17 levels characterize patients with CAAG and gNET and confirms the frequent coexistence of CAAG with other autoimmune diseases.

Topics: Adolescent; Adult; Aged; Autoimmune Diseases; Biomarkers; Diagnosis, Differential; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Neuroendocrine Tumors; Pepsinogen A; Pepsinogen C; Prevalence; Retrospective Studies; ROC Curve; Stomach Neoplasms; Young Adult

Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterised by destruction of gastric oxyntic mucosa AIM: To explore gastric histopathological evolution in a cohort of AAG patients over a prolonged follow-up METHODS: Single centre prospective study enrolling consecutive patients with histologically confirmed AAG between 2000 and 2018. All AAG patients undergoing endoscopic follow-up every 1-3 years were classified as having stages 1, 2 or 3 according to atrophy severity (mild, moderate and severe). AAG patients with either glandular or neuroendocrine dysplasia/neoplasia were classified as having stage 4. Disease stage progression, and changes in serum anti-parietal cell antibody (PCA), chromogranin A and gastrin-17 were assessed.. In total, 282 AAG patients (mean age 60.3 years; F:M ratio 2.4:1; median follow-up 3 years, interquartile range 1-7) were enrolled. All patients with stages 1 or 2 progressed to stage 2 or 3 over time with a steady trend (P = .243) and regression from a severe to a milder stage was never noticed. Disease progression of patients with stages 1 or 2 occurred within the first 3 years. PCA positivity rate did not change over time. Stage 3 patients had higher gastrin-17 levels compared to patients with stages 1 and 2 (median 606 vs 295 pg/mL; P < .001). In stage 3, the hazard ratio for the risk of developing stage 4 was 6.6 (95% CI 1.5-29; P = .001).. AAG is a steadily progressive disease, in which stages 1 and 2 always progress to stage 3. The risk of developing a complicated disease stage is greater in patients with more severe gastric lesions.

Topics: Adult; Aged; Autoimmune Diseases; Disease Progression; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Neuroendocrine Tumors; Prospective Studies; Severity of Illness Index; Stomach Neoplasms

Chronic autoimmune gastritis (CAG) is a continuum of histological changes in gastric mucosa including: atrophy, intestinal metaplasia, dysplasia and finally, the occurrence of a neoplasm (gastric Neuroendocrine Tumors -NETs- and adenocarcinoma). The association with Hashimoto and Graves-Basedow disease is known as the thyrogastric autoimmune syndrome. While Helicobacter pylori (Hp) infection may be associated with CAG, the role of the gastric microbiota is ill-defined. The gastric hypochlorhydria determines a malabsorption of different micronutrients (iron, magnesium, calcium, vitamin B12) as well as drugs (thyroxine, etc.). Pernicious anemia is favoured by the deficit of parietal intrinsic factor that contributes to B12 malabsorption. Serology for Hp, serum pepsinogen I/II, increased gastrin levels, the presence of parietal cell antibodies and intrinsic factor antibodies may reveal CAG. High definition endoscopy associated with virtual chromoendoscopy seems promising for CAG diagnosis and follow-up. NETs type 1 treatment includes: endoscopic and surgical resection, somatostatin analogues and the recent availability of netazepide, a gastrin antagonist. We review herein advances in the treatment and diagnosis of CAG and associated autoimmune disorders, which may involve, in a multidisciplinary way, all practitioners.. La gastrite chronique auto-immune (GAI) est un continuum d’altérations de la muqueuse gastrique incluant : atrophie, métaplasie intestinale, dysplasie et, enfin, la survenue d’une néoplasie (tumeurs neuroendocrines [NETs] gastriques et adénocarcinome). L’association avec la maladie de Hashimoto et de Graves-Basedow est connue comme syndrome thyrogastrique auto-immun. Alors que l’Helicobacter pylori (Hp) peut s’associer avec la GAI, le rôle du microbiote gastrique est mal défini. L’hypochlorhydrie gastrique détermine une malabsorption de micronutriments (fer, magnésium, calcium, vitamine B12) et de médicaments (thyroxine et autres). L’anémie de Biermer est favorisée par le déficit de production du facteur intrinsèque pariétal, contribuant à la malabsorption de B12. Un rapport diminué de pepsinogène I/II, une augmentation de la gastrine, la présence d’anticorps anti-cellule pariétale, les anticorps anti-facteur intrinsèque et la sérologie pour Hp contribuent à révéler précocement le diagnostic de GAI. L’endoscopie haute définition, associée à la chromoendoscopie virtuelle, semble prometteuse dans le diagnostic et dans le suivi. Le traitement des NETs gastriques de type 1, favorisées par la GAI, inclut : la résection endoscopique/chirurgicale, les analogues de la somatostatine et l’antagoniste de la gastrine nétazépide. Nous résumons ici les avancées diagnostiques et thérapeutiques dans la GAI et dans les affections associées : elles impliquent, de façon multidisciplinaire, l’ensemble des praticiens.

Topics: Autoimmune Diseases; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans

Our group observed the first case of synchronous gastric neuroendocrine tumor (NET) and duodenal gastrinoma with autoimmune chronic atrophic gastritis (CAG), in the absence of Helicobacter pylori infection. Demographic, clinical, endoscopic, and pathologic data were abstracted from the electronic medical record at Mount Sinai Hospital from 2013 to 2015. The patient's anonymity was carefully protected, and informed consent was obtained for publication of protected health information. A 53-year-old woman with hypertension presented to Mount Sinai Hospital in June 2013 for a second opinion for management of gastric and duodenal NETs. After evaluation by gastroenterology and surgery, repeat upper endoscopy with ultrasound and fine-needle aspiration revealed multiple diminutive type I gastric NETs and 2 duodenal NETs, against a background of autoimmune CAG, with biopsy pathology negative for H. pylori. She subsequently underwent a transduodenal resection of the duodenal NETs, confirming low-grade, gastrin-positive, stage T2 duodenal NET. On routine follow-up over the next 2 years, clinical, radiographic, and endoscopic surveillance revealed no recurrent or metastatic gastric or duodenal disease. This first report of synchronous duodenal gastrinoma and gastric NET in the setting of autoimmune CAG can broaden our understanding of gastric NET pathophysiology.

Topics: Autoimmune Diseases; Chronic Disease; Duodenal Neoplasms; Female; Gastrinoma; Gastrins; Gastritis, Atrophic; Humans; Hypertension; Middle Aged; Neuroendocrine Tumors; Stomach Neoplasms

Autoimmune gastritis patients may have autonomic nerve dysfunction. The goal of our study was to explore the predictive value of two scoring systems in the differentiation of altered autonomic nerve function in autoimmune gastritis patients.. Seventy-five patients with autoimmune gastritis were evaluated by using cardiovascular reflex tests in order to delineate autonomic nerve function. Data were analyzed by using two laboratory-based scoring systems: "global score" (hemoglobin, mean corpuscular volume, gastrin, vitamin B12, and chromogranin A) and "simple score" (hemoglobin, mean corpuscular volume, gastrin) in order to discriminate deranged and normal autonomic nerve function.. Mean "simple" and "global" scores were significantly higher in subjects with altered autonomic dysfunction than in subjects with normal autonomic function (3.55±1.88 vs. 0.908±0.409, p<0.001 and 5.95±2.07 vs 2.46±1.28, p<0.001, respectively). Receiver operatör characteristic (ROC) analysis revealed that the optimum "simple score" cutoff point was 0.75 with a sensitivity of 86.7% and specificity of 92.3% for discriminating autoimmune gastritis patients with autonomic nerve dysfunction from patients with normal autonomic nerve function [area under the curve (AUC): 88.3, positive predictive value (PPV): 97.5% and negative predictive value (NPV): 66.6%; 95% confidence interval (CI), 88.4-99.7].. Simple score and global score have a high predictive value in the assessment of autoimmune gastritis patients with autonomic nerve dysfunction. These scoring systems may help physicians while evaluating autoimmune gastritis patients for the existence of autonomic nerve dysfunction instead of complex cardiovascular reflex tests.

Topics: Area Under Curve; Autoimmune Diseases; Autonomic Nervous System; Autonomic Nervous System Diseases; Chromogranin A; Erythrocyte Indices; Gastrins; Gastritis; Hemoglobins; Humans; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Vitamin B 12

Pernicious anemia (PA) develops from atrophic gastritis due to autoimmune destruction of parietal cells and results in achlorhydria, vitamin B12 and iron deficiencies, anemia, neurologic deficits, and premalignant and malignant stomach lesions. We report the presentation, diagnosis and gastric complications of PA in patients from an endocrinology practice.. Thirty-four patients (31 female, 3 male) with PA who underwent esophagogastroduodenoscopy (EGD) or gastrectomy were identified. Pertinent clinical, laboratory, and pathology findings were reviewed and summarized.. The mean age of patients was 58.6 ± 14.2 years; the onset of PA was age 50.2 ± 15.3 years. Anemia reflected vitamin B12 and/or iron deficiencies. Parietal cell antibodies (PCA) were detected in 97% of patients, and intrinsic factor blocking antibody (IFBA) was found in 52%. Fasting gastrin and chromogranin A levels were elevated (1,518.0 ± 1,588.3 pg/mL, and 504.9.1 ± 1,524.9 ng/mL respectively). Autoimmune or immunologic diseases (AIDs) were present in 32/34 patients. Stomach pathology showed premalignant or malignant lesions in 26 patients, including gastric neuroendocrine tumors (GNETs) in 6 and adenocarcinoma in 1. One patient presented with neurologic symptoms and subacute combined degeneration of the posterior column of the spinal cord.. PA should be suspected in patients with unexplained anemia or neurologic symptoms. The diagnosis of PA relies on fasting gastrin and gastric auto-antibody testing, in addition to hematologic evaluation. EGD with measurement of gastric pH and biopsies of the fundus and antrum identifies patients with achlorhydria, atrophic gastritis, and premalignant and malignant stomach lesions. EGD surveillance of patients with high-risk stomach lesions is recommended.. AID = autoimmune or immunologic disease; EGD = esophagogastroduodenoscopy; GNET = gastric neuroendocrine tumor; IFBA = intrinsic factor blocking antibody; PA = pernicious anemia; PCA = parietal cell antibody; T1D = type 1 diabetes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Autoimmune Diseases; Endoscopy, Digestive System; Female; Gastrectomy; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Retrospective Studies; Young Adult

Elderly patients with autoimmune gastritis might have different symptoms than those of young patients. The aim of the present study was to compare presented symptoms and laboratory parameters associated with autoimmune gastritis in both old and young age groups.. A total of 355 patients with autoimmune gastritis were stratified into two groups: 65 years or older (n = 119, mean age 69.47 ± 5.027 years), and under 65 years (n = 236, mean age 45.79 ± 10.51 years). These two groups were then evaluated and compared by means of clinical symptoms, concurrent autoimmune diseases, serum gastrin, vitamin B

Topics: Adult; Age Distribution; Aged; Analysis of Variance; Autoimmune Diseases; Cohort Studies; Female; Gastrins; Gastritis; Humans; Male; Middle Aged; Multivariate Analysis; Prevalence; Prognosis; Retrospective Studies; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Vitamin B 12

To assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence of Helicobacter pylori infection.. Patients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histology and H. pylori testing. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies against H. pylori and cytotoxin-associated gene A protein were determined in all patients. Antibodies against parietal cells and intrinsic factor were determined in patients with advanced (moderate to severe) OGA. Areas under the receiver operating characteristic curves (AUCs) were calculated for serum biomarkers and compared with histology.. Overall, 34 patients (8.9%) had advanced OGA by histology (22 women, age 61±15 years). Current or past H. pylori infection and AIG were present in 14/34 and 22/34 patients, respectively. H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 6.3; 95% CI 1.3 to 29.8), severe corpus atrophy (OR 10.1; 95% CI 1.9 to 54.1) and corpus intestinal metaplasia (OR 26.9; 95% CI 5.3 to 136.5) compared with H. pylori-positive patients with advanced OGA. Antrum atrophy was present in 39% of H. pylori-negative AIG patients. The diagnostic performance of G17, PG I and PGI/II was excellent for AIG patients (AUC=0.83, 0.95 and 0.97, respectively), but limited for H. pylori-positive patients with advanced OGA (AUC=0.62, 0.75 and 0.67, respectively).. H. pylori-negative AIG has a distinct clinical, morphological and serological phenotype compared with advanced OGA in H. pylori gastritis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrophy; Autoimmune Diseases; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Humans; Male; Middle Aged; Pepsinogen A; Prospective Studies; Young Adult

Several biomarkers have been proposed for the diagnosis of autoimmune atrophic gastritis (AAG), but at the present there is no appropriate testing strategy for the disease.. The aim of this study was to develop and validate a laboratory score able to address the diagnosis of AAG in a general practice setting.. We prospectively evaluated a number of serum biomarkers (vitamin B12, mean corpuscular volume, hemoglobin, gastrin, and chromogranin A levels) in a case-control population and built 2 biochemical scores, the first with all the parameters [Global Score (GS)], and the second as the best statistical combination of them [Simple Score (SS)]. In the second phase we validated the score that proved to be more efficient on a random population referred to our center (Gastroenterology Outpatient Clinic).. Both models turned out to be reliable in detecting patients with suspected AAG, showing excellent accuracy [area under the receiver operating curve (AUC-ROC) 0.94; 95% confidence interval (CI), 0.91-0.97 for GS and AUC-ROC 0.93; 95% CI, 0.89-0.86 for SS]. The SS proved to be more convenient because of its accessibility and availability in a general setting and its low cost. The validation of the SS showed a sensitivity of 85.7% (95% CI, 57.2-98.2) and a specificity of 83.7% (95% CI, 74.2-90.89).. Herein, we describe 2 nonexpensive and reliable score models, particularly the SS, that can be applied in daily medical practice for identifying patients potentially affected by AAG.

Topics: Adult; Aged; Area Under Curve; Autoimmune Diseases; Biomarkers; Case-Control Studies; Chromogranin A; Erythrocyte Indices; Female; Gastrins; Gastritis, Atrophic; Hemoglobins; Humans; Logistic Models; Male; Middle Aged; Prospective Studies; ROC Curve; Vitamin B 12

Whole-lung lavage (WLL) remains the standard therapy for pulmonary alveolar proteinosis (PAP), a process in which accumulated surfactants are washed out of the lung with 0.5-2.0 l of saline aliquots for 10-30 wash cycles. The method has been established empirically. In contrast, the kinetics of protein transfer into the lavage fluid has not been fully evaluated either theoretically or practically. Seventeen lungs from patients with autoimmune PAP underwent WLL. We made accurate timetables for each stage of WLL, namely, instilling, retaining, draining, and preparing. Subsequently, we measured the volumes of both instilled saline and drained lavage fluid, as well as the concentrations of proteins in the drained lavage fluid. We also proposed a mathematical model of protein transfer into the lavage fluid in which time is a single variable as the protein moves in response to the simple diffusion. The measured concentrations of IgG, transferrin, albumin, and β2-microglobulin closely matched the corresponding theoretical values calculated through differential equations. Coefficients for transfer of β2-microglobulin from the blood to the lavage fluid were two orders of magnitude higher than those of IgG, transferrin, and albumin. Simulations using the mathematical model showed that the cumulative amount of eliminated protein was not affected by the duration of each cycle but dependent mostly on the total time of lavage and partially on the volume instilled. Although physicians have paid little attention to the transfer of substances from the lung to lavage fluid, WLL seems to be a procedure that follows a diffusion-based mathematical model.

Topics: Aged; Albumins; Algorithms; Autoimmune Diseases; beta 2-Microglobulin; Bronchoalveolar Lavage Fluid; Female; Gastrins; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunoglobulin G; Kinetics; Male; Middle Aged; Models, Biological; Protein Transport; Pulmonary Alveolar Proteinosis; Pulmonary Surfactant-Associated Protein D; Serum Albumin; Transferrin

Optimal management and treatment of type-1 gastric carcinoids is under debate.. This prospective study evaluates the outcome of patients with recurrent type-1 gastric carcinoids treated with somatostatin analogues.. From 2000 to 2013, among a population of 107 chronic atrophic gastritis patients, 25 (20% males, median age 62 years) developed type-1 gastric carcinoids and underwent regular clinical and endoscopic follow-up (median 77 months, range 6-165) after the initial treatment. Those patients showing recurrent disease were treated with somatostatin analogues until carcinoid disappearance.. 12/25 patients (33% males, median age 65 years) showed recurrent gastric carcinoids and were treated with somatostatin analogues for a median duration of 12 months. Median gastrin and chromogranin A levels, which were 802 pg/mL and 33 U/L, respectively, decreased to 299 pg/mL (p=0.002) and 15.6 U/L (p=0.001) at the end of the treatment. Gastric carcinoids disappeared after a median length of treatment of 12 months. After a median time of 19.5 months from somatostatin analogues discontinuation, 4/12 patients (25% males, median age 56 years) showed a further recurrence. A new cycle of treatment was performed successfully.. This study confirms that type-1 gastric carcinoids are a recurring disease and somatostatin analogues, administered on 12-month cycles, represent an effective treatment.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Autoimmune Diseases; Carcinoid Tumor; Chromogranin A; Cohort Studies; Female; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Octreotide; Peptides, Cyclic; Prospective Studies; Somatostatin; Stomach Neoplasms; Treatment Outcome

The aim of this study was to investigate the prevalence of autoimmune gastritis, enterochromaffin-like cell (ECL-cell) hyperplasia and gastric neuroendocrine neoplasms type 1 (GNEN1) in patients with autoimmune thyroid disease.. Prospective observational study in a single institutional study.. One hundred and twenty patients with autoimmune thyroid disease were consecutively recruited from the Endocrine Unit. Upper gastrointestinal tract endoscopy (UGE) and biochemical parameters for autoimmune thyroid disease and autoimmune gastritis were assessed at recruitment and annually thereafter in patients with a mean follow-up of 37·5 ± 14·4 months. Autoimmune gastritis was defined by the presence of antiparietal cell antibodies (APCA) and histological confirmation after UGE. Serum gastrin and chromogranin Α were also measured.. One hundred and eleven patients had Hashimoto's thyroiditis and nine Graves' disease. Autoimmune gastritis was identified in 40 (38 with Hashimoto's thyroiditis and two with Graves' disease) patients all of whom had increased levels of gastrin and chromogranin Α; Helicobacter pylori infection was histologically identified in 15 of 40 (37·5%) patients. Six patients had isolated nodular ECL-cell hyperplasia and one mixed nodular and linear ECL-cell hyperplasia [7 of 40 (17·5%)]. Only increased gastrin (P = 0·03) levels predicted the presence ECL-cell hyperplasia. A GNEN1 developed in one patient with nodular ECL-cell hyperplasia after 39 months of follow-up.. Concomitant autoimmune gastritis was found in 33·3% of patients with autoimmune thyroid disease, 17·5% of whom had ECL-cell hyperplasia that evolved to GNEN1 in one (2·5%). Larger studies with longer follow-up are needed to define the incidence of GNEN1 in patients with autoimmune thyroid disease and ECL-cell hyperplasia and potential implications.

Topics: Aged; Autoimmune Diseases; Chromogranin A; Endoscopy; Enterochromaffin-like Cells; Female; Gastrins; Gastritis; Hashimoto Disease; Helicobacter Infections; Humans; Male; Middle Aged; Neuroendocrine Tumors; Phenotype; Prevalence; Prospective Studies; Risk; Stomach Neoplasms; Thyroid Diseases

Topics: Autoimmune Diseases; Chromogranin A; Female; Gastrectomy; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Gastritis, Atrophic; Humans; Hyperplasia; Middle Aged; Mucin-6; Neuroendocrine Tumors; Stomach; Stomach Neoplasms; Synaptophysin

The gastric hormone ghrelin is known as an important factor for energy homeostasis, appetite regulation and control of body weight. So far, ghrelin has mainly been examined as a serological marker for gastrointestinal diseases, and only a few publications have highlighted its role in local effects like mucus secretion. Ghrelin can be regarded as a gastroprotective factor, but little is known about the distribution and activity of ghrelin cells in pathologically modified tissues. We aimed to examine the morphological changes in ghrelin expression under several inflammatory, metaplastic and carcinogenic conditions of the upper gastrointestinal tract. In particular, autoimmune gastritis showed interesting remodeling effects in terms of ghrelin expression within neuroendocrine cell hyperplasia by immunohistochemistry. Using confocal laser microscopy, the gastrin/cholecystokinin receptor (CCKB) could be detected on normal ghrelin cells as well as in autoimmune gastritis. Functionally, we found evidence for a physiological interaction between gastrin and ghrelin in a primary rodent cell culture model. Additionally, we gathered serological data from patients with different basic gastrin levels due to long-term autoimmune gastritis or short-term proton pump inhibitor treatment with slightly reactive plasma gastrin elevations. Total ghrelin plasma levels showed a significantly inverse correlation with gastrin under long-term conditions. Autoimmune gastritis as a relevant condition within gastric carcinogenesis therefore has two effects on ghrelin-positive cells due to hypergastrinemia. On the one hand, gastrin stimulates the proliferation of ghrelinpositive cells as integral part of neuroendocrine cell hyperplasia, while on the other hand, plasma ghrelin is reduced by gastrin and lost in pseudopyloric and intestinal metaplastic areas. Ghrelin is necessary for the maintenance of the mucosal barrier and might play a role in gastric carcinogenesis, if altered under these pre neoplastic conditions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Autoimmune Diseases; Child; Child, Preschool; Down-Regulation; Duodenum; Esophagus; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Ghrelin; Humans; Infant; Male; Middle Aged; Rats; Rats, Wistar; Receptor, Cholecystokinin B; Stomach Neoplasms; Young Adult

Autoimmune gastritis (AIG) may predispose to gastric carcinoid tumors or adenocarcinomas and may also cause unexplained iron and/or vitamin B(12) deficiency. The aims of this study were to explore clinical manifestations, endoscopic findings and laboratory features of patients with AIG.. 109 patients with AIG were enrolled into the study. In addition to demographic and clinical data, gastric lesions, serum gastrin, vitamin B(12), antiparietal cell antibody (APA), current Helicobacter pylori status, and anti-H. pylori IgG were also investigated.. The mean age of the patients was 53.06 ± 12.7 years (range 24-81; 72 (66.1%) women). The most common main presenting symptom was abdominal symptoms in 51 patients, consultation for iron and/or vitamin B(12) deficiency in 36, and non-specific symptoms including intermittent diarrhea in 15 patients. Endoscopic lesions were detected in 17 patients, hyperplastic polyps in 8, gastric carcinoid tumor in 4, fundic gland polyps in 3, and adenomatous polyps in 2 patients. H. pylori was negative in all patients in biopsy specimens; however, anti-H. pylori IgG was positive in 30 (27.5%) patients. 91 patients (83.4%) were positive for APA.. In patients with AIG, the main symptoms prompted for clinical investigation were: abdominal symptoms, iron/B(12) deficiency and non-specific symptoms. 20% of patients with AIG had various gastric lesions including type I gastric carcinoids. None of the patients were positive for H. pylori by means of invasive tests; however, anti-H. pylori IgG was found in 27.5% of patients. Patients referring with non-specific abdominal symptoms such as bloating, diarrhea and iron/B(12) deficiency should be investigated for the presence of AIG.

Topics: Adenomatous Polyps; Adult; Age Factors; Aged; Aged, 80 and over; Antibodies, Bacterial; Autoimmune Diseases; Carcinoid Tumor; Diarrhea; Female; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Iron; Iron Deficiencies; Male; Middle Aged; Parietal Cells, Gastric; Polyps; Sex Factors; Stomach Neoplasms; Vitamin B 12 Deficiency; Young Adult

Serum gastrin levels exceeding 1000pg/ml (normal, <100) usually raise the suspicion for a neuroendocrine tumor (NET) that secretes gastrin. Rarely, such elevated gastrin levels are seen in patients with pernicious anemia which most commonly is associated with autoimmune gastritis (AG). AG can occur concomitantly with other autoimmune disorders including lymphocytic colitis (LC). Gastrin stimulates enterochromaffin-like cells which increase histamine secretion. Histamine excess can cause diarrhea as can bacterial overgrowth or LC. We present a 57-year-old woman with diarrhea, sporadic epigastric pain, and bloating. She also had a history of interstitial cystitis and took pentosan polysulfate and cetirizine. She had no history of ulcers, renal impairment or carcinoid syndrome. Fasting serum gastrin was 1846pg/ml. Esophagoduodenal gastroscopy and biopsies revealed chronic gastritis and a pH of 7 with low stomach acid. Serum gastrin and plasma chromogranin A were suggestive of a gastrinoma or NET. Pernicious anemia was unlikely. Imaging studies did not reveal any tumor. Random colonic biopsy was compatible with LC, possibly explaining her diarrhea, although we also considered excessive histamine from elevated gastrin, bacterial overgrowth, and pentosan polysulfate which can cause diarrhea and be misleading in this setting, pointing to the diagnosis of gastrinoma. At 4year follow-up in 2012, fasting serum gastrin was 1097pg/ml and the patient asymptomatic taking only cetirizine for nasal allergies. This case illustrates that diarrhea may be associated with very high serum gastrin levels in the setting of chronic gastritis, LC, and interstitial cystitis (pentosan use), without clear evidence for a gastrinoma or NET. If no history of ulcers or liver metastases is present in such cases, watchful observation rather than an extensive/invasive and costly search for a NET may be justified. Considering the various forms of polyglandular syndrome, this may represent a variant and we here provide an algorithm for working up such patients, while also reviewing literature on the intertwined relationship between the immune and endocrine systems.

Topics: Autoimmune Diseases; Chronic Disease; Colitis, Lymphocytic; Diagnosis, Differential; Digestive System Neoplasms; Female; Gastrinoma; Gastrins; Gastritis, Atrophic; Humans; Middle Aged; Neuroendocrine Tumors

Gastrin has a cholecystokinetic action on gallbladder motility, and cholecystokinin and gastrin act directly on the smooth muscle of the gallbladder. The aim of this study was to investigate the effect of endogenous hypergastrinemia on gallbladder motility in patients with autoimmune gastritis.. Forty-one patients (29 females, 12 males; mean age, 46 years) with autoimmune gastritis and 29 healthy subjects (17 females, 12 males; mean age, 44.8 years) were enrolled in the study. Fasting and postprandial gallbladder volumes were measured ultrasonographically with the ellipsoid technique and the ejection fraction of the gallbladder was calculated from fasting and postprandial volumes. All subjects were investigated after 12 hours of fasting and 30 minutes after a standard test meal.. The gallbladder ejection fraction (%) of the patients with autoimmune gastritis was lower than that of the control group (46.06+/-18.28% vs 55.03+/-14.67%, P=0.032). There was no difference between patients with autoimmune gastritis and the control group in terms of the mean fasting gallbladder volume (30.38+/-12.85 vs 29.27+/-9.91 cm3, P=0.189) and the mean postprandial gallbladder volume (15.67+/-8.32 vs 13.44+/-7.69 cm3, P=0.258). Logistic regression analysis of baseline parameters revealed that "abdominal bloating" was a risk factor for the low gallbladder ejection fraction in autoimmune gastritis patients (P=0.045, F=4.40). In addition, logistic regression analysis of baseline parameters revealed that smoking (n=5, P=0.025, F=5.44) is a predictor of low gallbladder ejection fraction in patients with autoimmune gastritis.. Patients with endogenous hypergastrinemia have a low gallbladder ejection fraction compared with healthy controls. This study shows that at least part of upper gastrointestinal symptoms observed in this patient population may be due to altered gallbladder motility.

Topics: Adult; Aged, 80 and over; Autoimmune Diseases; Female; Gallbladder; Gastrins; Gastritis; Humans; Male; Middle Aged

To assess the predictive value for chronic autoimmune gastritis (AIG) of the combined assay of anti-parietal-cell antibodies (PCA), anti-intrinsic-factor antibodies (IFA), anti-Helicobacter pylori (Hp) antibodies, and measurement of blood gastrin.. We studied 181 consecutive patients with anemia, due to iron deficiency resistant to oral replacement therapy or to vitamin B12 deficiency.. 83 patients (45.8%) tested positive for PCA and underwent gastroscopy with multiple gastric biopsies. On the basis of the histological diagnosis, PCA-positive patients were divided into 4 groups: (1) 30 patients with chronic atrophic gastritis; they had high concentrations of PCA and gastrin and no detectable IFA; (2) 14 subjects with metaplastic gastric atrophy; they had high PCA, IFA, and gastrin; (3) 18 patients with nonspecific lymphocytic inflammation with increased PCA, normal gastrin levels, and absence of IFA; (4) 21 patients with multifocal atrophic gastritis with "borderline" PCA, normal gastrin, absence of IFA and presence of anti-Hp in 100% of the cases.. The assay of four serological markers proved particularly effective in the diagnostic classification of gastritis and highly correlated with the histological profile. As such, this laboratory diagnostic profile may be considered an authentic "serological biopsy."

Topics: Aged; Antibodies; Autoimmune Diseases; Biopsy; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Intrinsic Factor; Lymphocytes; Male; Middle Aged; Parietal Cells, Gastric; Serologic Tests

Antiparietal cells antibodies (APC-Ab) are commonly found in patients with autoimmune Addison's disease (AAD), usually pointing to autoimmune atrophic gastritis and pernicious anemia. The autoaggression to the gastric proton pumpmay result in a long-term hypergastrinemia, which predisposes to enterochromaffin-like cell hyper/dysplasia and gastric carcinoids.. We evaluated the clinical utility of assessing serum chromogranin A levels in patients with AAD.. Serum chromogranin A, gastrin, and gastric APC-Ab levels were determined in 40 patients with AAD using commercially available kits.. Serum chromogranin A and gastrin levels were found to be elevated in 27.5 and 22.5% of patients with AAD, respectively. The Addison's patients with elevated APC-Ab had significantly higher chromogranin A and gastrin levels, as compared to individuals with normal APC-Ab (chromogranin A: 128.00+/-123.08 vs 57.68+/-36.50 ng/ml, p=0.0036; gastrin: 141.38+/-191.43 vs 49.50+/-75.36 muU/ml, p=0.003). Additionally, the patients with AAD and coexisting elevated serum APC-Ab, contrary to those with normal levels, showed a significant correlation between the chromogranin A and gastrin concentrations (r=0.52, p=0.0092 vs r=0.211, p=0.43). Serum chromogranin A appeared also significantly correlated with APC-Ab levels (r=0.431, p=0.005).. In patients with autoimmune Addison's disease hyperchromograninemia and hypergastrinemia occur with a prevalence of 27.5 and 22.5%, respectively. Addison's patients with coexisting elevated gastric APC-Ab, particularly with elevated gastrin levels, are at risk of enterochromaffin-like cells hyper/dysplasia. Serum chromogranin A assessment may complement histology for the early diagnosis of gastric carcinoid in these patients.

Topics: Addison Disease; Adult; Aged; Autoimmune Diseases; Biomarkers; Chromogranin A; Enterochromaffin-like Cells; Female; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Parietal Cells, Gastric

To study the association between Helicobacter pylori (H. pylori) infection and autoimmune type atrophic gastritis.. Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology, immunoblot-based serology, and histology to reveal a past or a present H. pylori infection. In addition, serum markers for gastric atrophy (pepsinogen I, pepsinogen I/II and gastrin) and autoimmunity [parietal cell antibodies (PCA), and intrinsic factor (IF), antibodies] were determined.. Of the 14 patients with severe gastric atrophy, as demonstrated by histology and serum markers, and no evidence for an ongoing H. pylori infection, eight showed H. pylori antibodies by immunoblotting. All eight had elevated PCA and 4/8 also had IF antibodies. Of the six immunoblot-negative patients with severe corpus atrophy, PCA and IF antibodies were detected in four. Among the patients with low to moderate grade atrophic gastritis (all except one with an ongoing H. pylori infection), serum markers for gastric atrophy and autoimmunity were seldom detected. However, one H. pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis.. Signs of H. pylori infection in autoimmune gastritis, and positive autoimmune serum markers in H. pylori gastritis suggest an etiological role for H. pylori in autoimmune gastritis.

Topics: Aged; Autoantibodies; Autoimmune Diseases; Biomarkers; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoblotting; Immunoenzyme Techniques; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Pepsinogen C; Risk Factors; Severity of Illness Index; Vitamin B 12 Deficiency

Autoimmune metaplastic atrophic gastritis (AMAG) is an early manifestation of pernicious anemia that precedes the hematologic changes by years to decades. It is associated with metaplastic changes and neoplasms, including pyloric gland adenomas (PGAs). We investigated the frequency of PGAs and other lesions in all nonconsultation gastric biopsies and resections (1988 to 2008) diagnosed as AMAG. We further selected cases confirmed as AMAG by immunohistochemical identification of the gastric body (negative gastrin) and linear and nodular enterochromaffin-like cell hyperplasia (chromogranin). From this subset, all polyps and neoplasms were reviewed. We identified a total of 41,245 patients with gastric biopsies or resections from 46.7% males and 53.3% females comprising patients self-identified as 67.0% white, 23.6% African-American, 1.4% Asian, 0.8% non-White Hispanic, and 7.2% other or unknown. AMAG was diagnosed in 461 patients (1.1%), and had the following percentages based on race: 1.1% White, 1.3% African-American, 1.4% Asian, and 2.7% non-White Hispanic. The female:male ratio was 2:1 with an overall median age at presentation of 67.0 years. Of the 461 patients with AMAG, 143 had endoscopically identifiable lesions. These lesions (n=240) consisted of 179 polyps (138 hyperplastic polyps, 20 oxyntic mucosa pseudopolyps, 18 intestinal-type gastric adenomas, and 3 PGAs), 46 well-differentiated neuroendocrine neoplasms (carcinoid), 1 gastrointestinal stromal tumor, 3 lymphomas, and 11 adenocarcinomas. In summary, AMAG occurred with similar frequency across all racial groups. Although PGAs are associated with AMAG, they remain rare in the setting of AMAG.

Topics: Adenoma; Aged; Autoimmune Diseases; Baltimore; Biopsy; Chromogranins; Female; Gastrectomy; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Immunohistochemistry; Male; Metaplasia; Middle Aged; Polyps; Precancerous Conditions; Stomach; Stomach Neoplasms

To assess serologically diagnosed gastric body atrophy (GBA) by histology in a sample of the general population.. GBA is a precursor lesion in gastric cancer. Data on GBA in a primary health care community in the Netherlands have not been reported.. Thirty-four subjects of 997 consecutive adults from a Dutch family practice had serologic GBA, according to hypergastrinemia (>100 ng/L), hypopepsinogenemia A (<17 microg/L), and a low pepsinogen A/C ratio (<1.6). Two years later, 25 subjects of this group, agreed in serologic retesting and gastroscopy with biopsies for histologic assessment according to the Sydney system.. At serologic retesting, 20 of 25 subjects again fulfilled the serologic criteria of GBA. Histologic examination of the corpus biopsies showed advanced GBA in 18 subjects (75%) of 24 (1 subject had no corpus biopsies) and 17 of 19 (89%) subjects with repeated positive serology. After disclosure of serology results, reexamination of the biopsies revealed GBA also in the 2 patients with initially insufficient evidence of GBA, giving a concordance of 100% (19/19). One subject with normal serum gastrin at retesting had both antral and body atrophy giving a concordance between serologic and histologic GBA of 95% (19/20). No adenomatous polyps, tumors, or dysplastic alterations were found.. Identification by serology of asymptomatic patients with advanced GBA in primary care is adequately possible and useful in selecting for endoscopy.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Atrophy; Autoantibodies; Autoimmune Diseases; Biopsy; Chronic Disease; Cohort Studies; Diagnosis, Differential; Endoscopy; Female; Gastric Fundus; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Netherlands; Pepsinogens; Prevalence; Pyloric Antrum; Serologic Tests

Topics: Autoimmune Diseases; Diagnosis, Differential; Duodenal Neoplasms; Early Diagnosis; Gastrinoma; Gastrins; Gastritis, Atrophic; Humans; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Iron deficiency is a known complication of achlorhydria and may precede the development of pernicious anemia. Among 160 patients with autoimmune gastritis identified by hypergastrinemia and strongly positive antiparietal antibodies, we explored the overlap between 83 subjects presenting with iron deficiency anemia (IDA), 48 with normocytic indices, and 29 with macrocytic anemia. Compared with macrocytic patients, patients with IDA were 21 years younger (41 +/- 15 years versus 62 +/- 15 years) and mostly women. All groups had a high prevalence of thyroid disease (20%) and diabetes (8%) suggestive of the autoimmune polyendocrine syndrome. Stratification by age cohorts from younger than 20 years to older than 60 years showed a regular and progressive increase in mean corpuscular volume (MCV) from 68 +/- 9 to 95 +/- 16 fl, serum ferritin levels from 4 +/- 2 to 37 +/- 41 microg/L, gastrin level from 166 +/- 118 to 382 +/- 299 pM/L (349 +/- 247 to 800 +/- 627 pg/mL), and a decrease in cobalamin level from 392 +/- 179 to 108 +/- 65 pg/mL. The prevalence of Helicobacter pylori infection was 87.5% at age younger than 20 years, 47% at age 20 to 40 years, 37.5% at 41 to 60 years, and 12.5% at age older than 60 years. These findings challenge the common notion that pernicious anemia is a disease of the elderly and imply a disease starting many years before the establishment of clinical cobalamin deficiency, by an autoimmune process likely triggered by H pylori.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Anemia, Pernicious; Autoantibodies; Autoimmune Diseases; Disease Progression; Female; Gastrins; Gastritis; Humans; Male; Middle Aged; Reference Values; Vitamin B 12

The stimulation of gastric acid secretion from parietal cells involves both intracellular calcium and cAMP signaling. To understand the effect of increased cAMP on parietal cell function, we engineered transgenic mice expressing cholera toxin (Ctox), an irreversible stimulator of adenylate cyclase. The parietal cell-specific H(+),K(+)-ATPase beta-subunit promoter was used to drive expression of the cholera toxin A1 subunit (CtoxA1). Transgenic lines were established and tested for Ctox expression, acid content, plasma gastrin, tissue morphology, and cellular composition of the gastric mucosa. Four lines were generated, with Ctox-7 expressing approximately 50-fold higher Ctox than the other lines. Enhanced cAMP signaling in parietal cells was confirmed by observation of hyperphosphorylation of the protein kinase A-regulated proteins LASP-1 and CREB. Basal acid content was elevated and circulating gastrin was reduced in Ctox transgenic lines. Analysis of gastric morphology revealed a progressive cellular transformation in Ctox-7. Expanded patches of mucous neck cells were observed as early as 3 mo of age, and by 15 mo, extensive mucous cell metaplasia was observed in parallel with almost complete loss of parietal and chief cells. Detection of anti-parietal cell antibodies, inflammatory cell infiltrates, and increased expression of the Th1 cytokine IFN-gamma in Ctox-7 mice suggested that autoimmune destruction of the tissue caused atrophic gastritis. Thus constitutively high parietal cell cAMP results in high acid secretion and a compensatory reduction in circulating gastrin. High Ctox in parietal cells can also induce progressive changes in the cellular architecture of the gastric glands, corresponding to the development of anti-parietal cell antibodies and autoimmune gastritis.

Topics: Aging; Animals; Animals, Genetically Modified; Antibodies; Autoimmune Diseases; Cholera Toxin; Cyclic AMP; Disease Models, Animal; Gastric Acid; Gastrins; Gastritis; Gastritis, Atrophic; H(+)-K(+)-Exchanging ATPase; Mice; Mice, Inbred C57BL; Parietal Cells, Gastric; Promoter Regions, Genetic

Conventional endoscopic and radiographic methods fail to identify a probable source of gastrointestinal blood loss in about one third of males and post-menopausal females and in most women of reproductive age with iron deficiency anemia (IDA). Such patients, as well as subjects refractory to oral iron treatment, are often referred for hematologic evaluation.. Patient clinic, screened for non-bleeding gastrointestinal conditions including celiac disease (antiendomysial antibodies), autoimmune atrophic gastritis (hypergastrinemia with strongly positive antiparietal cell antibodies) and H. pylori infection (IgG antibodies confirmed by urease breath test).. The mean age of all subjects was 39+/-18 years, and 119 of 150 were females. We identified 8 new cases of adult celiac disease (5%). Forty IDA patients (27%) had autoimmune atrophic gastritis of whom 22 had low serum vitamin B12 levels. H. pylori infection was the only finding in 29 patients (19%), but was a common co-existing finding in 77 (51%) of the entire group. Refractoriness to oral iron treatment was found in 100% of patients with celiac disease, 71% with autoimmune atrophic gastritis, 68% with H. pylori infection, but only 11% of subjects with no detected underlying abnormality. H. pylori eradication in previously refractory IDA patients in combination with continued oral iron therapy resulted in a significant increase in hemoglobin from 9.4+/-1.5 (mean +/- 1SD) before, to 13.5+/-1.2 g/ dL (p<0.001 by paired t test) within 3 to 6 months.. The recognition that autoimmune atrophic gastritis and H. pylori infection may have a significant role in the development of unexplained or refractory IDA in a high proportion of patients should have a strong impact on our daily practice of diagnosing and managing IDA.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anemia, Iron-Deficiency; Antibodies, Bacterial; Autoantibodies; Autoimmune Diseases; Bacterial Proteins; Breath Tests; Celiac Disease; Child; Clarithromycin; Comorbidity; Drug Therapy, Combination; Female; Ferrous Compounds; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Omeprazole; Parietal Cells, Gastric; Prospective Studies; Urease; Vitamin B 12 Deficiency

H+/K+-ATPase beta-subunit-deficient mice (129/Sv background) display numerous pathologies in the stomach. Expression of the mutation in BALB/cCrSlc mice results in the development of an aberrant 'mucus-rich' cell population. 'Mucus-rich' cells have been described in stomachs of mice with autoimmune gastritis, a disease mediated by CD4+ T cells. Other pathological features of autoimmune gastritis are similar to those in H+/K+ beta-deficient mice and include a mononuclear cell infiltrate in the gastric mucosa, non-functional or absent parietal cells, depletion of zymogenic cells, hypergastrinaemia, and gastric unit hypertrophy caused by immature cell hyperplasia. The present study investigates further the aberrant gastric 'mucus-rich' cell lineage and analyses the mRNA expression of mucus cell products TFF1 and TFF2. 'Mucus-rich' cells stained for both acidic and neutral mucins, and with a TFF2-specific antibody. Stomachs from both models expressed decreased TFF1 mRNA and reciprocally increased TFF2 mRNA. The involvement of gastrin in regulating trefoil mRNA expression was also investigated using gastrin-deficient mice. In contrast to previous findings, gastrin did not positively regulate TFF1 mRNA expression, but there was possible augmentation of TFF2. Additionally, a clear role for inflammation was established involving both polymorphonuclear and mononuclear cells in these models, and a link was found between mucosal hypertrophy and increased interleukin-11 (IL-11) expression.

Topics: Animals; Autoimmune Diseases; Cytokines; Disease Models, Animal; Gastric Mucosa; Gastrins; Gastritis; Gene Expression Regulation; H(+)-K(+)-Exchanging ATPase; Hyperplasia; Hypertrophy; Interleukin-11; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Mucins; Muscle Proteins; Peptides; RNA, Messenger; Species Specificity; Trefoil Factor-1; Trefoil Factor-2

A prominent pathological feature of murine autoimmune gastritis is a pronounced mucosal hypertrophy. Here, we examined factors that may be responsible for inducing this hypertrophy. Because gastrin is known to be both an inducer of gastric mucosal cell proliferation and is elevated in autoimmune gastritis, mice deficient in gastrin were thymectomised at day 3 and assessed for autoimmune gastritis. Gastrin-deficient mice showed all the characteristic features of murine autoimmune gastritis, including gastric unit hypertrophy due to hyperproliferation and accumulation of immature epithelial cells, decreases in the number of zymogenic and parietal cells, and autoantibodies to the gastric H+/K+-ATPase. Hence, gastrin is not required for either the establishment of chronic gastritis or development of the typical pathological features of this disease. We also examined mRNA levels of a number of gastric mucosal growth factors in RNA samples from mice with hypertrophic autoimmune gastritis. Members of the Reg family, RegIIIbeta and RegIIIgamma, were greatly elevated in mice with hypertrophic gastritis, whereas RegI and amphiregulin (an EGF receptor ligand) were more modestly and/or inconsistently induced. These data demonstrate that induction of gastric mitogenic factors, such as members of the Reg family, can be achieved in inflammatory situations by gastrin-independent pathways. Members of the Reg family, in particular RegIIIbeta and RegIIIgamma, are good candidates to be involved in inducing the mucosal hyperproliferation in autoimmune gastritis. These findings are likely to be of relevance to other gastric inflammatory conditions.

Topics: Amphiregulin; Animals; Autoantibodies; Autoimmune Diseases; Chronic Disease; EGF Family of Proteins; Epidermal Growth Factor; ErbB Receptors; Gastric Mucosa; Gastrins; Gastritis; Gene Expression; Glycoproteins; Growth Substances; H(+)-K(+)-Exchanging ATPase; Heparin-binding EGF-like Growth Factor; Hypertrophy; Intercellular Signaling Peptides and Proteins; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Proteins; RNA, Messenger; Transforming Growth Factor alpha

This observation recalls that gastric phytobezoar should lead to a search for an underlying disease and that a iron deficiency can be associated and hide macrocytosis related to a vitamin B12 deficiency.. A 19 year-old woman consulted for asthenia. Microcyte anaemia associated with iron deficiency was diagnosed. Upper digestive endoscopy revealed severe, totally asymptomatic phytobezoar. Biological investigations revealed a vitamin B12 deficiency, high serum gastrin level and strong positivity for gastric antiparietal anti-cell antibodies, suggestive of an autoimmune gastritis. Total immunoglobulin A deficiency was also noted.. Autoimmune gastritis is responsible for megaloblastic anaemia (vitamin B12 deficiency) but can also provoke microcytic (iron-deficiency) anaemia due to insufficient absorption of the latter and related to gastric achlorhydria. Phytobezoar might also be related to achlorhydria and/or gastroparesia associated with autoimmune gastritis. Hence, autoimmune gastritis should be searched for when confronted with unexplained gastric bezoar or iron-deficiency anaemia.

Topics: Adult; Anemia, Iron-Deficiency; Autoimmune Diseases; Bezoars; Female; Gastrins; Gastritis; Humans; Plants; Vitamin B 12 Deficiency

To determine the frequency and significance of pancreatic acinar cells in the gastric oxyntic mucosa.. One hundred gastric oxyntic mucosal biopsy specimens from patients with chronic active gastritis (n = 30), multifocal atrophic gastritis (n = 15), autoimmune gastritis (n = 18), and normal gastric oxyntic mucosa (n = 37) were evaluated for the presence of pancreatic acinar cells. Formalin-fixed, paraffin-embedded tissues were stained with hematoxylin-eosin, and those positive for pancreatic acinar cells were immunostained with antibodies against trypsin and pancreatic amylase.. Eleven (11%) of 100 oxyntic mucosal tissue samples contained pancreatic acinar cells. These samples came from 9 of the 18 (50%) specimens of autoimmune gastritis, 1 of the 15 (6.6%) specimens of multifocal atrophic gastritis, and 1 of the 37 (2.7%) specimens of normal oxyntic mucosa. None of the samples with chronic active gastritis contained pancreatic acinar cells.. Pancreatic acinar cells were found in the oxyntic mucosa of patients with autoimmune gastritis significantly more frequently (P <.001) than in individuals with multifocal atrophic gastritis, normal oxyntic mucosa, or chronic active gastritis. Our study supports a metaplastic origin for pancreatic acinar cells in the oxyntic mucosa. Furthermore, detection of pancreatic acinar cells in the oxyntic mucosa of patients with gastritis strongly suggests an autoimmune pathogenesis.

Topics: Autoimmune Diseases; Carrier Proteins; Formaldehyde; Gastrectomy; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Atrophic; Glycoproteins; Helicobacter Infections; Helicobacter pylori; Humans; Lipase; Metaplasia; Pancreas; Paraffin Embedding; Parietal Cells, Gastric; Tissue Fixation

Long term Helicobacter pylori infection leads to atrophic gastritis but the relation between H pylori infection and autoimmune related atrophic gastritis (AIG) remains unclear. We studied the effects of H pylori infection on the pathophysiology of AIG in mice.. BALB/c nu/nu mice (n=40) with or without H pylori infection received splenocytes from neonatally thymectomised mice to induce AIG. Half of the mice were orally infected with H pylori prior to AIG induction. Histological findings, and local and systemic immune responses were serially evaluated.. Two and six months after transfer, parietal cells in uninfected mice were depleted while those in infected mice were well preserved. The degree of gland atrophy (p<0.01), hyperplasia (p<0.01), gastric pH (p<0.05), and serum gastrin levels of infected mice were significantly lower than those of uninfected mice. Serum antiparietal cell antibody levels gradually decreased in infected mice, and were significantly lower than those of uninfected mice at six months (p<0.05). Real time polymerase chain reaction studies revealed significantly higher interleukin 4 (p<0.05) and transforming growth factor beta (p<0.05) gene expression in the gastric mucosa in infected mice than in uninfected mice at both two and six months after AIG induction.. H pylori infection inhibited the development of AIG in mice. Th2-type immune responses and transforming growth factor beta in the gastric microenvironment might be involved in the inhibitory effects of H pylori infection on the development of AIG, in which Th1-type responses have an important role.

Topics: Animals; Antibodies; Autoimmune Diseases; Cytokines; Enzyme-Linked Immunosorbent Assay; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Hydrogen-Ion Concentration; Immunohistochemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Parietal Cells, Gastric; Polymerase Chain Reaction; RNA, Messenger; Up-Regulation

Autoimmune gastritis (AG) can be easily recognized when the histological features are fully developed, but recognizing AG before the complete loss of the oxyntic mucosa is more challenging. One feature of fully developed AG is enterochromaffin cell-like (ECL) hyperplasia, but its presence or absence in earlier stages of AG has not been fully evaluated. A retrospective study of biopsy specimens from 40 patients was performed; all of the patients were originally diagnosed with possible AG based on the presence of lymphocytic infiltration and damage to oxyntic glands and/or the presence of metaplastic epithelium that disproportionately involved the body mucosa. Nineteen cases had follow-up serological studies for anti-parietal cells and/or anti-intrinsic factor antibodies: 13 were positive and 6 negative. The remaining 21 cases were indeterminate because of incomplete testing. The histological findings were similar in the patients who were serologically positive and those who were indeterminate for AG. In all of these cases, the oxyntic mucosa showed lymphoplasmacytic infiltrates within the lamina propria with focal gland infiltration and damage. Sixty-five percent (22/34) of the cases showed intestinal and/or pyloric metaplasia, and 85% (29/34) showed parietal cell pseudohypertrophy. Chromogranin stains were performed in 11 of 13 cases with positive serological markers for AG, and all showed at least linear ECL cell hyperplasia. In contrast, none of the six cases with negative serological studies had linear ECL cell hyperplasia, P <.001. In conclusion, the following constellation of findings supports a diagnosis of AG before the complete loss of oxyntic mucosa: deep or diffuse lymphoplasmacytic infiltrates within the lamina propria with foci of gland infiltration and damage, epithelial metaplasia, parietal cell pseudohypertrophy, and ECL cell hyperplasia at the linear or greater level.

Topics: Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Female; Gastrins; Gastritis; Humans; Immunohistochemistry; Male; Middle Aged; Parietal Cells, Gastric

In Japan, most cases of gastric carcinoid tumor (GCT) are unassociated with either autoimmune gastritis (AIG) showing type-A chronic atrophic gastritis (CAG-A) or Zollinger-Ellison syndrome (ZES). However, the pathogenesis of this tumor remains unknown. Recent studies have determined that Helicobacter pylori infection induces gastric carcinoid in Mongolian gerbils and that H. pylori lipopolysaccharide exerts a mitogenic effect on ECL cells. We examined five patients with histologically diagnosed GCT, 40 patients with H. pylori-positive gastric ulcer (Hp+GU), 24 patients with H. pylori-positive duodenal ulcer (Hp+DU), and 12 patients with AIG showing CAG-A topographically. We compared the prevalence of H. pylori infection, and the levels of gastrin and pepsinogen (PG) in the serum of patients with GCT with those of patients with Hp+GU, or Hp+DU, and AIG. We also investigated the histological characteristics of the tumor and the gastric corpus mucosa in the GCT patients. The levels of serum gastrin and PG I and II were measured using an RIA kit. In all five (100%) patients with GCT, H. pylori infection was present, without any evidence of AIG or ZES. The serum levels of gastrin in the GCT patients were higher than those in either Hp+GU or Hp+DU patients and lower than those in the AIG patients. In contrast, serum PG I levels and the PG I/II ratio were lower in the GCT group than in the Hp+GU or Hp+DU groups. Histologically, all GCTs were ECL cell tumors and peritumoral corporal mucosal atrophy was observed in four of the five patients with GCT. In conclusions, H. pylori infection and hypergastrinemia were found in the patients with GCT without AIG. This finding suggests that H. pylori infection may induce corporal mucosal atrophy and hypergastrinemia that can produce a GCT with time.

Topics: Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Carcinoid Tumor; Duodenal Ulcer; Female; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Peptic Ulcer; Stomach Neoplasms

Previous studies have shown a high prevalence of gastric parietal cell antibodies (PCA) in type 1 diabetes, which can be accompanied by (sub)clinical autoimmune gastric disease. This study aimed to determine the grade of associated autoimmunity and to assess the pattern of prevalence of PCA by gender, age, duration of disease, age at onset of diabetes, and human leukocyte antigen (HLA) type in an adult type 1 diabetic population. Furthermore, to examine the clinical significance of being PCA positive, manifestations of gastric autoimmune disease were studied in PCA-positive and PCA-negative patients. The population studied consisted of 497 type 1 diabetics (men/women, 252/245; mean age, 40.8 +/- 12.1 yr; mean duration of disease, 16.4 +/- 10.4 yr; mean age at onset, 26.9 +/- 13.5 yr; mean hemoglobin A1c, 8.1 +/- 1.6%). Associated autoantibodies were present in 39% and PCA were present in 20.9% of the subjects, particularly in older patients. Gender, duration, and age at onset of diabetes did not influence the appearance of PCA. Antithyroid peroxidase antibodies (aTPO) were more frequent in PCA-positive patients than in those without PCA (33.6% vs. 22.4%; P = 0.025), suggesting an association between gastric and thyroid autoimmunity. We could demonstrate an association between PCA and the HLA DR5 haplotype (P = 0.001) as well, but not with HLA DR3 and/or DR4. In the PCA-positive group, iron deficiency anemia was detected in 15.4%, and pernicious anemia was found in 10.5% of subjects. These autoimmune gastric manifestations were significantly more prevalent in PCA-positive diabetics than in PCA-negative subjects, in whom the percentages were 6.9% and 0.5%, respectively (P = 0.01 and P < 0.0001). PCA were prevalent in 84.6% of patients with pernicious anemia. A gastroscopic and anatomopathological examination performed in a subgroup of 30 patients with gastric symptoms revealed atrophic gastritis in 13 of 14 PCA-positive patients and in 9 of 16 PCA-negative subjects (P = 0.04). PCA were present in 59.1% of patients with atrophic gastritis. In conclusion, a high prevalence of parietal cell antibodies and associated autoimmune gastric disease is present in PCA-positive type 1 diabetics, recommending its screening. Early detection of PCA and iron deficiency anemia, pernicious anemia, and atrophic gastritis and the subsequent care could reduce the morbidity of type 1 diabetes.

Topics: Adult; Aging; Anemia, Pernicious; Autoantibodies; Autoimmune Diseases; Diabetes Mellitus, Type 1; Female; Gastrins; Gastritis, Atrophic; Glycated Hemoglobin; HLA-DR1 Antigen; Humans; Iron; Male; Middle Aged; Parietal Cells, Gastric; Risk Factors; Sex Characteristics

This study aimed to investigate the cause of persistently increased serum gastrin concentration seen in some Graves' disease patients even when euthyroid during antithyroid drug treatment. The subjects studied consisted of three groups: 33 patients with a common-type of Graves' disease, 14 with triiodothyronine (T3)-predominant Graves' disease (characterized from previous studies as having potent immunologic abnormalities including greater concentrations of thyroid-stimulating antibodies together with larger goiter size), and a group of 20 normal subjects. Fasting serum gastrin concentrations in common Graves' disease patients were significantly higher than those of normal subjects (58.4 +/- 38.9 pmol/L vs. 37.8 +/- 18.9 pmol/L [mean +/- SD], p < 0.05). The serum gastrin concentrations were even greater in T3-predominant Graves' disease patients than common Graves' disease patients (162.9 +/- 224.0 pmol/L vs. 58.4 +/- 38.9 pmol/L, p < .05). Serum pepsinogen I (PGI) concentrations were significantly lower in the T3-predominant patient group than the common Graves' group (24.0 +/- 12.9 ng/mL vs. 39.7 +/- 19.6 ng/mL, p < .05). Serum ratios of PG I to PG II were significantly lower in the T3-predominant Graves' disease patients than normal subjects (3.59 +/- 2.66 vs. 5.97 +/- 1.56, p < .01). The ratios also had a significant (p < .05) inverse correlation with serum gastrin concentrations in T3-predominant Graves' disease patients. The results suggest that autoimmune gastritis is associated with Graves' disease, particularly in patients with potent thyroid-autoimmunity.

Topics: Adolescent; Adult; Autoimmune Diseases; Female; Gastrins; Gastritis; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Middle Aged; Pepsinogens; Triiodothyronine

Topics: Autoimmune Diseases; Endocrine Gland Neoplasms; Gastric Mucosa; Gastrins; Gastritis; Humans; Hyperplasia; Iatrogenic Disease; Pyloric Antrum

The influence of gastrin on the colonic mucosa is still uncertain. Some authors have suggested a stimulating effect on the growth of normal and malignant colonic epithelium, while others have shown no association between gastrin and neoplastic development.. To evaluate the effect of gastrin on colorectal cell proliferation, patients with chronic endogenous hypergastrinaemia underwent proctoscopy. Biopsy specimens were taken in order to study rectal cell kinetics.. Ten patients with chronic autoimmune gastritis (CAG), six patients with Zollinger-Ellison syndrome (ZES), and 16 hospital controls took part in this study. Patients with CAG and ZES had basal serum gastrin concentrations significantly higher than controls (p < 0.001).. Immunohistochemistry was performed on 3 microns sections of rectal biopsy specimens incubated with 5'-bromodeoxyuridine.. The percentage of proliferating cells in the entire crypts (overall labelling index) was similar in all the groups. However, the labelling frequency in the upper two fifths of the glands (phi h value) was significantly higher in patients with CAG or ZES compared with controls (p < 0.01 in both patient groups versus controls).. Endogenous hypergastrinaemia is associated with rectal cell proliferation defects, similar to those observed in conditions at high risk for colon cancer. The effect of the increased serum concentrations of gastrin on the colorectal mucosa after treatment with drugs inhibiting gastric acid secretion should be investigated.

Topics: Adult; Aged; Autoimmune Diseases; Cell Division; Chronic Disease; Colonic Neoplasms; Female; Gastrins; Gastritis; Humans; Immunohistochemistry; Male; Middle Aged; Rectum; Risk Factors; Zollinger-Ellison Syndrome

A now 54-year-old woman was 32 years ago found to have immune thrombocytopenia and 3 years ago ANA-positive and HBsAg-negative hepatitis with cirrhotic metaplasia. Numerous small asymptomatic carcinoids with marked hypergastrinaemia (1626 ng/l) were also first found 3 years ago. No gastrinoma could be found. Severe arthralgia was the main symptom on admission.. Gastroscopy revealed a polypoid carcinoid, 1 cm in diameter. There was total achlorhydria. No pernicious anaemia or carcinoid syndrome was found.. Total gastrectomy with construction of a jejunal substitute stomach was performed. Histology showed typical chronic-atrophic gastritis type A, all stages of an argyrophilic endocrine cell hyperplasia, as well as microcarcinoidosis and multicentric carcinoid, in part with submucosal infiltration and lymph node metastases. Immunohistology revealed immune reaction for the global endocrine marker. No specific hormones were demonstrable in the carcinoid cells. The postoperative course was without complications. Serum gastrin levels have since been normal.. The case confirms the possibility of an achlorhydria-hypergastrinaemia-carcinoid sequence. Now new stage-related therapeutic guidelines for this disease are needed.

Topics: Achlorhydria; Autoimmune Diseases; Carcinoid Tumor; Female; Follow-Up Studies; Gastrectomy; Gastrins; Gastritis, Atrophic; Gastroenterostomy; Humans; Jejunum; Lymphatic Metastasis; Middle Aged; Stomach; Stomach Neoplasms; Time Factors

Topics: Aged; Animals; Atrophy; Autoantibodies; Autoimmune Diseases; Case-Control Studies; Female; Gastric Mucosa; Gastrins; Humans; Immunity, Mucosal; Intestines; Liver Diseases; Male; Metaplasia; Middle Aged; Parietal Cells, Gastric; Rats

A 48-year-old woman with type II diabetes developed fatigue, arthralgia and myalgia. A few weeks later she was found to have hepatomegaly. The erythrocyte sedimentation rate was raised (53/93 mm), as were liver enzyme activities (GOT 186 U/l; GPT 240 U/l; gamma-GT 199 U/l), the gamma-globulin levels (40.7%;IgG 4470 mg/dl, IgA 698 mg/dl, IgM 245 mg/dl), antinuclear antibodies and antibodies against double-strand DNA, smooth muscles and actin. Laparoscopy revealed small-nodular liver cirrhosis. The autoimmune hepatitis was treated with prednisolone (initially 60 mg daily, then reduced to 10 mg daily) and azathioprine (initially 100 mg daily, reduced to 50 mg daily). The symptoms markedly improved. But one year later, during follow-up examination, gastric polyps were found, excised and histologically found to be carcinoid. The gastrin level was raised to 765 pg/ml. Another year later the liver cirrhosis had advanced further and the type A gastritis was still present, but there was no sign of carcinoid recurrence.

Topics: Autoimmune Diseases; Azathioprine; Carcinoid Tumor; Cholangiopancreatography, Endoscopic Retrograde; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Endoscopy, Digestive System; Female; Follow-Up Studies; Gastrins; Gastritis; Hepatitis; Humans; Liver Cirrhosis; Middle Aged; Prednisolone; Stomach Neoplasms

Data on risk factors for bone loss in chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC) are scanty and/or conflicting.. Bone mineral density (BMD) in the distal forearm was measured using single-photon absorptiometry in 39 patients with CAH and 32 patients with PBC. We also attempted to identify risk factors for bone loss by means of a questionnaire and through a wide range of biochemical analyses.. In the CAH patients BMD is inversely related to the duration of steroid treatment and to age at menarche. In the PBC patients there was a strong correlation between BMD and serum gastrin concentrations.. Bone loss in CAH is to some extent explained by steroid treatment and delayed menarche. Bone loss in PBC may be reduced by increased calcitonin secretion induced by gastrocalcin.

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Bone Density; Diet; Female; Gastrins; Hepatitis C; Hepatitis, Chronic; Humans; Liver Cirrhosis, Biliary; Male; Menarche; Middle Aged; Osteoporosis; Radionuclide Imaging; Risk Factors

A 63-year-old woman was diagnosed as autoimmune gastritis by the presence of serum antibody against alpha-subunit of gastric H+,K(+)-ATPase. The patient did not have pernicious anemia, but showed achlorhydria, marked hypergastrinemia, enterochromaffin-like cell hyperplasia and an extremely high histidine decarboxylase activity in the gastric fundic mucosa. Intragastric acidification by infusion of hydrochloric acid via a nasogastric tube induced a transient reduction of serum gastrin level and fundic mucosal histidine decarboxylase activity. A marked increase in fundic mucosal histidine decarboxylase activity as well as hypergastrinemia appears to be the pathophysiologic response to achlorhydria caused by autoimmunity against gastric H+,K(+)-ATPase.

Topics: Achlorhydria; Autoimmune Diseases; Enterochromaffin Cells; Female; Gastric Fundus; Gastric Mucosa; Gastrins; Gastritis; Graves Disease; H(+)-K(+)-Exchanging ATPase; Histidine Decarboxylase; Humans; Hyperplasia; Middle Aged; Parietal Cells, Gastric; Polyps; Stomach Neoplasms

The presence of autoimmune gastritis was investigated in 54 women with postpartum thyroiditis. Parietal cell antibodies (PCA) specific against H+, K(+)-adenosine triphosphatase (EC 3.6.1.36) were found in 18 women during pregnancy; in 10 of them, a 2-9-fold increase in the PCA level was observed in the postpartum period. At a 5-year follow-up, the initially PCA-positive women still had elevated antibody levels. Hypergastrinemia and low pepsinogen levels were noted in 4 women. In 2 of these women low serum vitamin B12 levels had developed. In 6 of 9 PCA-positive women examined by gastroscopy, biopsy specimens from the gastric body mucosa contained mononuclear cells, mainly T lymphocytes (CD3+) and macrophages (Leu-M3+) combined with an aberrant epithelial expression of HLA-DR. In four patients with chronic gastritis, all parietal cells, as defined by a specific monoclonal antibody, were found to have immunoglobulin G (IgG) deposits by a double-immunostaining method. Three of them had microscopic evidence of atrophy, whereas in 1 patient the body mucosa was intact. In 1 further patient with intact glands at histological examination, the basolateral membrane of some oxyntic glands was coated with IgG. The selective in situ deposition of antibodies associated with histologically intact parietal cells may support the concept that specific autoantibodies participate in the early pathogenesis of parietal cell destruction.

Topics: Adenosine Triphosphatases; Adult; Antibodies; Autoimmune Diseases; Biopsy; Female; Fluorescent Antibody Technique; Follow-Up Studies; Gastric Mucosa; Gastrins; Gastritis; H(+)-K(+)-Exchanging ATPase; Humans; Immunoglobulin A; Immunoglobulin G; Iron; Pepsinogens; Pregnancy; Puerperal Disorders; Thyroiditis, Autoimmune; Vitamin B 12

Topics: Autoimmune Diseases; Campylobacter Infections; Chronic Disease; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Atrophic; Humans; Parietal Cells, Gastric

The authors tried to clarify relations between autoimmune gastritis and isolated atrophic corpus gastritis by bioptic corporal and antral examinations from 150 probands as well as examinations of gastrin in serum and parietal cell antibody tests. Only 30% of all patients examined with isolated atrophic gastritis of the corpus part revealed criteria of an autoimmune gastritis. Therefore investigations of antibodies against parietal cells are necessary to mark off both clinical pictures. This differentiation seems to be necessary regarding the high risk of gastric cancer following an autoimmune gastritis.

Topics: Autoantibodies; Autoimmune Diseases; Biopsy; Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Atrophic; Gastroscopy; Humans; Parietal Cells, Gastric

Gastric biopsies, and measurements of fasting serum gastrin levels and titers of antihuman parietal cell antibodies have been performed in 65 unselected patients with vitiligo. Histologic evidence of autoimmune atrophic gastritis has been obtained in 10 cases (15%), who were all positive for the antibodies and who had elevated gastrin levels. The study of gastric secretion after pentagastrin stimulation, performed in 7 of these patients, showed a markedly reduced acid output. The present study provides definite evidence of the association of autoimmune atrophic gastritis with a proportion of vitiligo cases and suggests the need for surveillance of these patients in terms of gastric neoplasia.

Topics: Adolescent; Adult; Autoantibodies; Autoimmune Diseases; Female; Gastric Acid; Gastrins; Gastritis; Gastritis, Atrophic; Humans; Male; Middle Aged; Vitiligo

Topics: Adolescent; Adult; Autoimmune Diseases; Female; Gastrins; Gastritis; Gastritis, Atrophic; Humans; Hyperthyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Middle Aged; Parietal Cells, Gastric

In 118 patients with histological proven chronic gastritis, was performed a study of seric antibodies against parietal cells (ACCP), following the indirect inmuno-fluorescence method. The results were positives in 36 cases (30%). Four positives cases were found in 40 normal controls (10%), two of them were compensated diabetics, one have the thyrohyoid Hashimoto's disease, and the remainder, brother of a patient with chronic gastritis, was a positive ACCP. A major positiveness (44.4%) was obtained in 9 cases of gastric atrophy than in 65 cases with atrophic gastritis (32%) and in 44 cases of superficial gastritis (25%); although due to the few cases of gastric atrophy regarding other histological types, conclusions cannot be obtained about the incidence of ACCP and histological variety of chronic gastritis. If we do group the patients according to their acid secretory debit, 53 achlorhydric patients had a positiveness of ACCP of 45%, while over 63 with decreased secretory capability, only 18.4%, was positive. The distribution by age groups, shows a major incidence of ACCP about the 4th and 5th decade of life. Thirty seven patients with chronic atrophic gastritis and achlorhydria, and seven with chronic superficial gastritis and hypochlorhydria, besides the antibodies study were on a basal dosage of gastrinemia and antral endoscopic biopsy, finding out that, achlorhydric patients (15 on 19) with normal or slightly altered antrus, have gastrinemia (222 +/- 123 Pgo/oo) and the majority of patients with normal gastrinemia (32 +/- 16 pgo/oo) have more important antral lesions. The ratio between antral histology and ACCP in auto--immune gastritis (Type A), conciliates only partially with the observation by Strickland et al., as only 52.4% of achlorhydric patients and ACCP have a normal antrus or al least with mild lesions. Our results suggest the possibility of that on auto--immune gastritis could act other pathogenic factors of antral lesion.

Topics: Adult; Aged; Autoantibodies; Autoimmune Diseases; Chronic Disease; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Pyloric Antrum

Autoantibodies that react exclusively with the gastrin-secreting cell of human antrum have been detected by immunofluorescence in eight of 106 patients with histologic evidence of chronic atrophic gastritis, Type B, involving mainly the antrum. These antibodies were of the IgG class and of low titer. However, follow-up studies one to two years later showed persistently positive reactions, despite symptomatic treatment. These data support the concept of an autoimmune variant of chronic "antral" gastritis, Type B.

Topics: Adult; Aged; Atrophy; Autoantibodies; Autoimmune Diseases; Chronic Disease; Female; Fluorescent Antibody Technique; Follow-Up Studies; Gastrins; Gastritis; Humans; Immunoglobulin G; Male; Middle Aged; Pyloric Antrum

Out of a score of patients known as suffering from Addison's disease, tuberculosis was the cause in 7, and their serum fasting gastrin levels were normal, averaging 52 pg/ml. For the 14 remaining cases, with the auto-immune variety of the disease, there were high gastrin levels in 3; in 2 out the 11 others, with values within the normal range, there was total achlorhydria. Could it be that gastrin-secreting cells might occasionally be involved in auto-immune endocrine disorders?

Topics: Addison Disease; Autoimmune Diseases; Female; Gastrins; Humans; Male

Seventeen patients with dermatitis herpetiformis were tested for gastric hydrochloric acid secretion. Seven were found to be achlorhydric. Atrophic gastritis in these patients probably had an auto-immune pathogenesis, as judged by elevated serum gastrin level, high prevalence of antibodies against gastric parietal cells and antrum sparing of the gastric atrophy. This type of atrophic gastritis is considered to indicate a precursor state to pernicious anemia.

Topics: Adult; Aged; Autoantibodies; Autoimmune Diseases; Bile Acids and Salts; Dermatitis Herpetiformis; Female; Gastric Juice; Gastrins; Gastritis; Humans; Male; Middle Aged; Secretory Rate; Stomach

Elevation in fasting serum gastrin levels was found in three patients being evaluated for persistent upper abdominal pain without radiographic evidence of peptic ulcer disease. Fiberoptic endoscopy of the upper gastrointestinal tract in each patient revealed characteristic changes of chronic atrophic gastritis. Gastric biopsies showed diffuse chronic inflammation in the lamina propria, a decrease in the number of parietal cells, and "intestinalization" of gastric mucosa. Total achlorhydria was demonstrated after a maximal histalog stimulus; however, serum levels of vitamin B12 and Schilling test values were normal in all three patients. Parietal cell antibodies were found in the serum in all patients in a dilution of 1:20 to 1:80. These cases represent autoimmune (type A) chronic atrophic gastritis and should be distinguished from chronic simple (type B) gastritis, in which serum gastrin levels are normal and no parietal cell antibodies are found in the serum. Patients with autoimmune gastritis should be observed at frequent intervals for the occurrence of pernicious anemia or gastric carcinoma.

Topics: Achlorhydria; Adult; Antacids; Atrophy; Autoantibodies; Autoimmune Diseases; Chronic Disease; Female; Gastrectomy; Gastrins; Gastritis; Humans; Middle Aged

Fasting gastrin levels in serum were measured in 49 patients with different types of chronic gastritis and in matched controls. In 15 patients with established pernicious anaemia the mean (+/- S.E. of mean) level of gastrin was greatly raised (699 +/- 99 pg/ml). In 17 patients with chronic atrophic gastritis, seropositive for parietal cell antibody but with adequate vitamin-B(12) absorption, the level was also raised (476 +/- 74 pg/ml). By contrast, in "simple" atrophic gastritis seronegative for parietal cell antibody the gastrin levels were significantly lower for both diffuse atrophic gastritis (129 +/- 31 pg/ml) and multifocal gastritis (14 +/- 4 pg/ml). These levels were similar to those in the controls (46 +/- 7 pg/ml).The mechanism of the raised gastrin levels remains uncertain, but neither achlorhydria nor in vivo action of the parietal cell antibody wholly accounted for the hypergastrinaemia.We conclude that hypergastrinaemia is characteristic of gastritis associated with autoimmune reactions to gastric antigens and pernicious anaemia and that a raised serum gastrin is a useful marker of the type of gastritis that tends to progress to the gastric lesion of pernicious anaemia. The findings suggest that this type of gastritis is an essentially different disease from "simple" atrophic gastritis, and the differences in gastrin levels may be due to sparing of the antral mucosa in the autoimmune type but not in "simple" gastritis.

Topics: Achlorhydria; Aged; Anemia, Pernicious; Antibodies; Antigens; Autoimmune Diseases; Chronic Disease; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Vitamin B 12