Autoimmune Gastritis Patients Research Articles

P-088 - Genetic polymorphisms and PG1/PG2 and G17 levels can predict gastric carcinoids in autoimmune atrophic chronic gastritis patients

P-088 - Genetic polymorphisms and PG1/PG2 and G17 levels can predict gastric carcinoids in autoimmune atrophic chronic gastritis patients

Utility of a laboratory score in the prediction of gastric emptying in autoimmune gastritis patients

Objectives: Patients with autoimmune gastritis may have symptoms suggestive of delayed gastric emptying. The aim of this study was to explore the predictive value of two scoring systems in the differentiation of delayed gastric emptying in patients with autoimmune gastritis.Methods: About 154 patients (106 women) with autoimmune gastritis whose gastric emptying test were available, were analyzed 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, and gastrin) in order to discriminate delayed and normal gastric emptying.Results: The mean ‘simple score’ was 4.82 ± 0.94 for autoimmune gastritis patients with delayed gastric emptying and 0.72 ± 0.60 for patients with normal gastric emptying (p < 0.001). The mean ‘global score’ was 7.42 ± 0.81 for autoimmune gastritis patients with delayed gastric emptying and 1.176 ± 0.98 (p < 0.001) for patients with normal gastric emptying. There was also a positive correlation between severity of symptoms of patients with autoimmune gastritis and global (r = 0.83, p < 0.001) and simple scores (r = 0.81, p < 0.001).Conclusion: This model may help physicians, while evaluating autoimmune gastritis patients and deciding which patients need gastric emptying test. Gastric emptying study should be ordered in patients who are fulfilling the criteria proposed by these scoring systems.

Distinct metaplastic and inflammatory phenotypes in autoimmune and adenocarcinoma-associated chronic atrophic gastritis.

Autoimmune gastritis (AIG) and adenocarcinoma-associated chronic atrophic gastritis (CAG) are both associated with oxyntic atrophy, but AIG patients demonstrate an increased risk of carcinoid tumors rather than the elevated risk of adenocarcinoma observed with CAG. We therefore sought to compare the characteristics of the metaplastic mucosa in AIG and CAG patients. We examined markers for metaplasia (spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal metaplasia) as well as proliferation (Ki67) and immune cell populations (neutrophils, macrophages, and eosinophils) in gastric sections from 16 female patients with autoimmune thyroiditis and AIG and 17 patients with CAG associated with gastric adenocarcinoma. Both AIG and CAG patients demonstrated prominent SPEM and intestinal metaplasia. However, AIG patients displayed significantly lower numbers of infiltrating macrophages and significantly reduced mucosal cell proliferation as compared to CAG patients. These findings indicate that, while both AIG and CAG patients display prominent oxyntic atrophy and metaplasia, the AIG patients do not show proliferative metaplastic lineages that would predispose to adenocarcinoma.

Upper gastrointestinal symptoms in autoimmune gastritis: A cross-sectional study.

Autoimmune gastritis is often suspected for its hematologic findings, and rarely the diagnosis is made for the presence of gastrointestinal symptoms. Aims of this cross-sectional study were to assess in a large cohort of patients affected by autoimmune gastritis the occurrence and the pattern of gastrointestinal symptoms and to evaluate whether symptomatic patients are characterized by specific clinical features.Gastrointestinal symptoms of 379 consecutive autoimmune gastritis patients were systematically assessed and classified following Rome III Criteria. Association between symptoms and anemia pattern, positivity to gastric autoantibodies, Helicobacter pylori infection, and concomitant autoimmune disease were evaluated.In total, 70.2% of patients were female, median age 55 years (range 17–83). Pernicious anemia (53.6%), iron deficiency anemia (34.8%), gastric autoantibodies (68.8%), and autoimmune disorders (41.7%) were present. However, 56.7% of patients complained of gastrointestinal symptoms, 69.8% of them had exclusively upper symptoms, 15.8% only lower and 14.4% concomitant upper and lower symptoms. Dyspepsia, subtype postprandial distress syndrome was the most represented, being present in 60.2% of symptomatic patients. Univariate and multivariate analyses showed that age <55 years (OR 1.6 [CI:1–2.5]), absence of smoking habit (OR 2.2 [CI:1.2–4]), and absence of anemia (OR 3.1 [CI:1.5–6.4]) were independent factors associated to dyspepsia.Autoimmune gastritis is associated in almost 60% of cases with gastrointestinal symptoms, in particular dyspepsia. Dyspepsia is strictly related to younger age, no smoking, and absence of anemia.

Factors associated with elevated serum chromogranin A levels in patients with autoimmune gastritis.

Chromogranin A is an important tool in the diagnosis of neuroendocrine tumors. Autoimmune gastritis is an autoimmune disorder marked by hypergastrinemia, which stimulates enterochromaffin-like cell proliferation. Chromogranin A is also elevated in autoimmune gastritis patients with a different level of increase in each patient. The goal of this study is to explore constituents that influence serum chromogranin A levels in autoimmune gastritis patients. One hundred and eighty-eight autoimmune gastritis patients and 20 patients with type I gastric carcinoid tumors were analyzed retrospectively and compared to 110 functional dyspepsia patients in terms of factors that might affect serum chromogranin A levels. The mean serum chromogranin A level was 171.17±67.3 ng/mL in autoimmune gastritis patients (n=62) without enterochromaffin-like cell hyperplasia, and 303.3±102.82 ng/mL in patients (n=126) with enterochromaffin-like cell hyperplasia (p<0.001). The presence of corpus atrophy (p=0.026, OR: 5.03, CI 95%: 1.21-20.88, β=1.61) and presence of enterochromaffin-like cell hyperplasia (p=0.017, OR: 6.59, CI 95%: 1.4-31.08, β=1.88) were found as risk factors associated with serum chromogranin A level. Factors influencing raised serum chromogranin A levels in autoimmune gastritis were the presence of ECL cell hyperplasia and serum gastrin levels. Serum chromogranin A levels maybe helpful in distinguishing autoimmune gastritis patients and gastric carcinoid type I from the control group, but not useful in the differentiation of individuals with autoimmune gastritis from patients with gastric carcinoids.

Polyautoimmunity in autoimmune gastritis

ObjectivesAutoimmune gastritis may be associated with other organ-specific autoimmune disorders, but the prevalence of this association is not entirely quantified. The aims of this study were to investigate the prevalence of autoimmune disorders and evaluate the factors that might affect this association in patients with autoimmune gastritis. MethodsA total of 320 patients with autoimmune gastritis were retrospectively studied and data on concomitant autoimmune diseases, serum gastrin and chromogranin A levels, anti-Hp IgG, antiparietal cell antibodies, presence of enterochromaffin-like cell hyperplasia and gastric atrophy were gathered for each patient and associations between autoimmune gastritis and studied parameters were explored through descriptive statistics and logistic regression analysis. ResultsOf the 320 atrophic body autoimmune gastritis patients, 171 (53.4%) had an associated autoimmune disorder. Autoimmune thyroiditis was the most common concurrent disease, diagnosed in 116 patients (36.2%). Multivariate analysis showed that, presence of enterochromaffin cell hyperplasia (odds ratio [OR] 9.445, 95% confidence [CI]: 4.42–20.22), serum gastrin (OR 3.1, 95% CI: 1.46–6.60) and serum chromogranin A (OR 4.14, 95% CI: 2.01–8.52) levels remained significantly associated with the coexistence of an autoimmune disease. ConclusionsConcurrent autoimmune diseases are common in patients with autoimmune gastritis. Autoimmune thyroiditis is the most encountered disease. These data suggest that patients with autoimmune gastritis should be investigated for the presence of an autoimmune disease, in particular patients with enterochromaffin cell hyperplasia and those with serum gastrin and chromogranin A levels above cut-off values.

Relationships between autonomic nerve function and gastric emptying in patients with autoimmune gastritis.

Autonomic nervous system dysfunction exists in autoimmune diseases. Symptoms of autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any autonomic dysfunction exists in autoimmune gastritis patients, and if so, to clarify the relationship between the autonomic nervous dysfunction, delayed gastric emptying, and gastrointestinal symptoms. 75 patients (50 women, mean age 56.73±11.77) diagnosed with autoimmune gastritis were investigated by means of autonomic nervous system and gastric emptying tests. All patients underwent a standardized scintigraphic gastric emptying study and five tests evaluating autonomic nervous system. Patients with autonomic nervous system dysfunction were then analyzed and compared by means of existence of delayed gastric emptying and gastrointestinal symptoms. 62 patients had autonomic nervous system dysfunction (14 mild, 40 moderate, and 8 severe autonomic dysfunction). The mean total score of autonomic tests was 3.85±2.35. Total autonomic score of patients (n=60) with delayed gastric emptying was significantly higher than patients (n=15) with normal gastric emptying (4.68±1.7 vs. 1.53±0.58, p<0.001). Mean gastroparesis cardinal symptom index was significantly higher in patients (n=60) with delayed gastric emptying half-time compared to patients (n=15) with normal gastric emptying half-time (1.89±1.16 vs 0.4±0.3, p<0.001). Most of patients with autoimmune gastritis also have autonomic nerve dysfunction. There is a close relationship between autonomic nervous system dysfunction and delayed gastric emptying. Gastroparesis cardinal symptom index has a high sensitivity and specificity in predicting both autonomic nerve function and delay in gastric emptying.

Oxyntic gastric atrophy in Helicobacter pylori gastritis is distinct from autoimmune gastritis

AimTo assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence of Helicobacter pylori infection.MethodsPatients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014...

Tu1722 Does Antibody Producibility Affect the Serum Anti-Helicobacter pylori Immunoglobulin G Antibody Titer?

Tu1722 Does Antibody Producibility Affect the Serum Anti-Helicobacter pylori Immunoglobulin G Antibody Titer? Hyun Ah Chung*, Sun-Young Lee, Jeong Hwan Kim, Hyung Seok Park, Chan Sup Shim, in-Kyung Sung Department of Internal Medicine, Kunkuk University School of Medicine, Seoul, Korea (the Republic of) Background/Aims: Serum antibody titer differs according to the antibody producibility of the host. Hepatitis B vaccination is performed to all Koreans in the infancy or childhood supported by the national insurance, but some do not produce hepatitis B virus surface antibody (HBsAb) after the vaccination. The aim of this study was to elucidate whether the serum anti-H. pylori IgG antibody titer is related to serum HBsAb titer in Korean adults. Methods: Consecutive Korean adults with positive Giemsa staining who underwent serum pepsinogen (PG) assay, anti-H. pylori IgG antibody test, hepatitis B virus surface antigen (HBsAg)/antibody test, and endoscopic biopsy for H. pylori evaluation on the same day were included. Subjects were excluded if they were under 20 years old, showed a positive HBsAg finding, had a recent history of medication, or were in immunocompromised state. Results: Of 158 Korean adults who fulfilled the study inclusion criteria, 107 subjects (67.7%) showed marked H. pylori infiltration based on the Updated Sydney System, whereas 33 (20.9%) and 18 (11.4%) showed moderate and mild infiltration. The serum anti-H. pylori IgG antibody titer was significantly correlated with the amount of H. pylori infiltration on gastric biopsy (p!0.001), PG II concentration (pZ0.012), and PG ratio (p!0.001), but not to the serum HBsAb titer (pZ0.649) and PG I concentration (pZ0.115). The serum HBsAb titer in the subjects with marked H. pylori infiltration on the gastric biopsy was not different from those of the subjects with moderate and mild H. pylori infiltration (pZ0.505). Conclusions: The serum anti-H. pylori IgG antibody titer is significantly linked to the bacterial load of the stomach regardless of the antibody producibility of the host. The serum anti-H. pylori IgG antibody test can be used for estimating the burden of bacteria in immunocompetent host with H. pylori infection. Tu1723 Difference of Micoromucosal Patterns of the Gastric Corpus Mucosa BetweenHelicobacter pylori-Associated and Autoimmune Gastritis Patient Noriya Uedo*, Ervin Toth, Ryu Ishihara, Tomofumi Akasaka, Noboru Hanaoka, Yoji Takeuchi, Koji Higashino, Artur Nemeth, Gabriele W. Johansson, Henrik Thorlacius, Hiroyasu Iishi Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Endoscopy, Skane University Hospital, Malmo, Sweden; Surgery, Skane University Hospital, Malmo, Sweden Background: Helicobacter pylori (H. pylori)-associated gastritis and autoimmune gastritis are two major entities of chronic atrophic gastritis. However, characteristic of micromucosal pattern observed by magnifying endoscopy of these diseases has not been fully investigated. Aim of this study is to compare magnifying endoscopic appearance between H. pylori-associated and autoimmune gastritis. Methods: Six H. pylori naive, 14 H. pylori-associated gastritis and 7 autoimmune gastritis patients were enrolled in this study. A videoendoscope, EVIS GIFFQ260Z, that can be used in high-resolution white light, autofluorescence (AFI) and magnifying narrow band imaging (M-NBI) modes was used to evaluate mucosal features. Extent of mucosal atrophy in the corpus was determined as extent of greenish areas in AFI. A 2 2 cm area at the lesser curvature of the corpus about 4 cm proximal to the angulus was set as the region of interest for evaluation of micromucosal patterns. The micromucosal patterns were classified into Foveola and Groove type according to magnifying chromoendoscopic and M-NBI findings. The Foveola type mucosa was characterized as mucosa with round, oval, or short linear foveolae (gastric pits) on magnifying chromoendoscopy. On M-NBI, it had network of dark brown subepithelial capillary that surround light brown epithelium. The Groove type mucosa was characterized by mucosal crests or papillae that were divided by continuous grooves on magnifying chromoendoscopy, and had light brown epithelium that encase dark brown subepithelial capillary. Proportion of the micromucosal patterns were categorized as, Foveola O80%; Foveola 50-80%; Groove 50-80%; and Groove O80%. Biopsy sample was taken from the region of interest to evaluate histological grade of gastritis. Results: All H. pylori naive patients had purple corpus mucosa and the micromucosal pattern was Foveola type. 10 of 14 (71%) patients with H. pylori-associated gastritis showed medium to large greenish atrophic mucosa at the lesser curvature of the corpus, and 13 of 14 (93%) had various proportion of groove type mucosa. All autoimmune gastritis patients had large area of greenish mucosa in the entire corpus but most (O80%) of micromucosal pattern was Foveola type. The biopsy specimen in H. pylori-associated gastritis patients had higher grade of intestinal metaplasia than that in autoimmune gastritis patients. Conclusion: Micromucosal pattern of the gastric corpus mucosa in H. pylori associated-gastritis patients was unlike to that of autoimmune gastritis patients suggesting different pathogenesis of these diseases AB572 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 5S : 2015 Summary of endoscopic appearances

Single nucleotide polymorphisms related to vitamin B12 serum levels in autoimmune gastritis patients with or without pernicious anaemia

BackgroundAutoimmune gastritis may present as pernicious anaemia arising from vitamin B12 malabsorption, but also with iron deficiency anaemia due to iron malabsorption. These different clinical presentations might have a genetic basis. Single nucleotide polymorphisms associated with vitamin B12 levels have not been investigated in autoimmune gastritis. AimsTo determine the frequency of single nucleotide polymorphisms related to vitamin B12 levels in autoimmune gastritis patients, with or without pernicious anaemia, compared to healthy controls. Methods14 single nucleotide polymorphisms associated with vitamin B12 levels were selected from literature. 83 autoimmune gastritis patients (43 with and 40 without pernicious anaemia) and 173 controls were enrolled. Genomic DNA was extracted from peripheral blood leukocytes. Genotyping was performed using Sequenom MALDI-TOF mass spectrometry iPLEX platform. ResultsTCN2 (rs9606756) GG genotype, related with lower vitamin B12 levels, was found in 3 (3.6%) autoimmune gastritis patients (2 with pernicious anaemia), but in none of controls (p=0.02). FUT6 (rs3760776) AA genotype was present in four (4.8%) autoimmune gastritis patients (all pernicious anaemia) and three (1.7%) controls (p=0.007). ConclusionA genetic variant of TCN2 (rs9606756) related to lower vitamin B12 levels was more frequent in pernicious anaemia patients compared to controls, showing the plausibility of genetic factors determining the possible clinical manifestation of autoimmune gastritis.

The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors

Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p < 0.001) and red cell distribution width (16.11 ± 3.04 vs. 13.41 ± 0.95%, p < 0.001) were significantly higher in autoimmune gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.

Interleukin‐21 and tumor necrosis factor‐α are critical for the development of autoimmune gastritis in mice

Autoimmune gastritis (AIG), an organ-specific autoimmune disease, is accompanied by achlorhydria, pernicious anemia, gastric carcinoid tumors, and gastric cancer. Patients with AIG initially respond to corticosteroids but have a great potential to relapse after treatment is withdrawn. This study examines the roles of cytokines in order to identify potential therapeutic options for AIG patients. Using a mouse model of AIG, we monitored disease progression and administered antibodies in vivo to block cytokines. We developed a mouse model of AIG with early onset and rapid progression in which neonatal thymectomy (NTx) was performed on programmed cell death 1-deficient (PD-1(-/-) ) mice on the BALB/c background. Using NTx-PD-1(-/-) mice, we found that in AIG lesions, interferon-γ, and tumor necrosis factor (TNF)-α together with interleukin-21 (IL-21) were highly expressed in the inflamed gastric mucosa. In addition, as with the injection of dexamethasone, in vivo administration of either anti-TNF-α or anti-IL-21 suppressed the development of AIG in NTx-PD-1(-/-) mice. These data reveal the essential role of IL-21 in the development of AIG and suggest that in addition to corticosteroids, anti-TNF-α as well as anti-IL-21 have the potential to induce the remission of AIG, offering additional therapeutic options for AIG patients.

Effect of endogenous hypergastrinemia on gallbladder volume and ejection fraction in patients with autoimmune gastritis

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.

Multiparametric Assessment of Vascular Function and Atherosclerosis in Patients with Autoimmune Gastritis: A Comparative Study

Patients with autoimmune gastritis might have accelerated atherosclerosis due to autoimmunity and chronic inflammation. Endothelial dysfunction often precedes manifest atherosclerosis. The aim of the present study was to evaluate the risk factors of early atherosclerosis by using several different techniques. A total of 99 patients with autoimmune gastritis were compared to 42 healthy age sex-matched subjects. Patients with a known risk factor for atherosclerosis were excluded. Intima-media thickness of the common carotid artery, pulse wave velocity and flow-mediated dilation of brachial artery were measured. Clinical data and laboratory parameters (serum gastrin, antiparietal cell antibody, anti-Hp IgG, serum vitamin B(12) and lipid profile) were also determined. Intima-media thickness (mm) of the carotid artery was significantly higher in autoimmune gastritis (0.062 ± 0.031 vs. 0.042 ± 0.007, P < 0.001) than in healthy individuals. Flow-mediated dilation was significantly lower in patients with autoimmune gastritis compared to control group (13.91 ± 6.68% vs. 20.37 ± 7.80%, P = 0.021) and there was a significant increase in pulse wave velocity (m/s) in autoimmune gastritis patients compared to controls (9.25 ± 3.42 vs. 6.40 ± 0.91, P = 0.001). Antiparietal cell antibody positivity (P = 0.05), low vitamin B(12) level (P = 0.05), and age (P = 0.002) were the predictors of high pulse wave velocity (>14 m/s). Patients with autoimmune gastritis may have an increased risk for the development of early atherosclerosis. As early preventive treatment for accelerated atherosclerosis is available, it is important to detect those patients with autoimmune gastritis who would benefit from such treatment.

Hypovitaminosis D as Predisposing Factor for Atrophic Type A Gastritis: a Case–Control Study and Review of the Literature on the Interaction of Vitamin D with the Immune System

1,25-Dihydroxyvitamin D displays immunoregulatory and anti-inflammatory properties, and the cells involved in innate and adaptive immune response express the vitamin D receptor and can both produce and respond to this hormone. This article aims at describing the complex immune regulatory role of vitamin D and depicting whether a correlation exists between atrophic type A gastritis and hypovitaminosis. We studied 62 autoimmune gastritis (AIG) patients and compared them to 54 lymphocytic gastritis patients, 21 Helicobacter pylori gastritis patients and 212 healthy subjects. We also statistically analyzed vitamin D concentration in 36,384 outpatients referred to our clinical laboratories. 25-Hydroxyvitamin D levels, the measurable metabolite used to determine vitamin D status in plasma, were measured by a chemiluminescent method. Average level of 25-OHD in AIG subjects was 9.8 ± 5.6 ng/mL (95% confidence interval (CI) 8.4-11.2), 11.1 ± 8.4 (CI 7.5-14.7) in H. pylori gastritis patients, 22.2 ± 13.5 (CI 18.6-25.8) in nonspecific lymphocytic gastritis patients, 21.3 ± 12.2 (CI 19.7-22.9) in healthy subjects, and 21.8 ± 13.1 (CI 21.7-21.9) in the 36,384 outpatients. Vitamin D levels in AIG patients were significantly lower than in patients with nonspecific gastritis or in the general population, supporting the hypothesis that hypovitaminosis D might be a risk factor for the development of autoimmune diseases. The low vitamin D concentration in H. pylori gastritis patients might act as predisposing factor for a more severe Th1-type aggression to the stomach epithelium.

Immunogenetic characteristics of patients with autoimmune gastritis

To explore whether predisposition to autoimmune gastritis (AIG) is found in human leukocyte antigen (HLA), cytokine or killer cell immunoglobulin-like receptor (KIR) gene variations. Twelve Finnish patients with autoimmune-type severe atrophy of the gastric corpus were included. The patients' serum was analyzed for pepsinogen I and Helicobacter pylori (H. pylori) antibodies. DNA was separated and the patients were genotyped for HLA-A, B, Cw, DRB1 and DQB1 antigens, and studied for single nucleotide polymorphisms for the following cytokines: interleukin (IL)-1 gene cluster, IL-2, IL-4, IL-6, IL-10, IL-12, interferon gamma, transforming growth factor beta, and tumor necrosis factor alpha. Variation in KIR genes was also explored. The results were compared with prevalence of the polymorphisms in Finnish or European populations. All patients had pepsinogen I levels below normal (mean: 11 microg/L, range: < 5 to 25 microg/L). Three patients had elevated H. pylori IgG antibodies, while H. pylori serology was negative in the rest of the patients. AIG patients carried significantly more often HLA-DRB1*04 (58%) and DQB1*03 (83%) than the general Finnish population did (28% and 51%, respectively; P = 0.045 and 0.034 by the Fisher's exact test). No patient was positive for HLA-B8-DRB1*03, a well-established autoimmune marker. Neither cytokine polymorphisms nor KIR gene variation showed association with AIG. As explored with modern DNA-based methods, HLA-DRB1*04 and DQB1*03 alleles, but not HLA-B8-DRB1*03, may predispose to AIG.

Chronic Gastritis and Bone Mineral Density in Women

We conducted a cross-sectional study of bone mineral density in women with Helicobacter pylori gastritis or autoimmune gastritis. Eighty-five patients were enrolled: 24 patients (mean age 55.2 +/- 13.5 years) with autoimmune gastritis, 34 patients (mean age 63.7 +/- 7.3 years) with H. pylori gastritis, and 27 H. pylori-negative patients with normal gastric mucosa (mean age 62.5 +/- 7.0 years). Gastric mucosa was evaluated by histology and immunohistochemistry. Bone mineral density was measured by dual-energy X-ray absorptiometry. Autoimmune gastritis patients presented severe gastric body mucosa atrophy, based on the absence of parietal cells in 15 (62.5%) patients and the presence of only scattered parietal cells in the remaining nine (37.5%) patients. Among the H. pylori gastritis patients, 21 (62%) presented with different degrees of gastric mucosa atrophy. Bone mineral densities (mean +/- SD, g/mm(2)) were not different among patients with autoimmune gastritis and H. pylori gastritis and the controls. Our results suggest that H. pylori-associated gastritis and autoimmune gastritis would not to be risk factors for decreased bone mineral density in women.

Immunoblotting reveals signs of infection in all autoimmune atrophic gastritis patients

Immunoblotting reveals signs of infection in all autoimmune atrophic gastritis patients

Gastric carcinoid tumors without autoimmune gastritis in Japan: a relationship with Helicobacter pylori infection.

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.

H+,K+-ATPase (proton pump) is the target autoantigen of Th1-type cytotoxic T cells in autoimmune gastritis

Background & Aims: The proton pump H+,K+-adenosine triphosphatase (H+,K+-ATPase) of parietal cells is the major humoral autoantigen in both human and experimental autoimmune gastritis (AIG) characterized by an inflammatory infiltrate in the gastric mucosa and loss of parietal cells. The aim of this study was to detect H+,K+-ATPase–specific T cells in the gastric mucosa of patients with AIG and to define their functional properties. Methods: In vivo–activated T cells from the infiltrates of the gastric mucosa of 5 patients with AIG were isolated and cloned. The ability of gastric T-cell clones to proliferate and to produce cytokines in response to H+,K+-ATPase, as well as their expression of B-cell help, perforin-mediated cytotoxicity, and Fas-Fas ligand–mediated apoptosis in target cells, were assessed. Results: A proportion (25%) of the CD4+ clones from the gastric corpus of AIG patients proliferated in response to porcine H+,K+-ATPase. Most of these clones (88%) showed a Th1 profile, whereas a few secreted both Th1 and Th2 cytokines. Virtually all of the H+,K+-ATPase–specific clones produced tumor necrosis factor α and provided substantial help for B-cell immunoglobulin production, and most of them expressed perforin-mediated cytotoxicity against antigen-presenting cells and induced Fas-Fas ligand–mediated apoptosis in target cells. Conclusions: Activation of proton pump–specific Th1 cytotoxic/proapoptotic T cells in the gastric mucosa can represent an effector mechanism for the target cell destruction in AIG.GASTROENTEROLOGY 2001;120:377-386