Helicobacter pylori, parietal cell antibodies and autoimmune gastropathy in type 1 diabetes mellitus

Abstract

Background: Fifteen to 20% of type 1 diabetic patients exhibit parietal cell antibodies (PCA), which are associated with autoimmune gastritis, hypochlorhydria, iron deficiency and pernicious anaemia. Aim: To examine whether Helicobacter pylori infection could explain the high prevalence of PCA and autoimmune gastropathy in diabetes. If so, H. pylori eradication could prevent autoimmune gastritis. Methods: In 229 type 1 diabetics (M/F: 135/94; age: 41 ± 12 years) PCA were measured. H. pylori infection was assessed by serology, urea breath test in all and by histology (updated Sydney system) in 88 subjects. Pentagastrin tests were performed in 42 patients. Results: Sixty‐nine patients were PCA‐positive. H. pylori infection was present in 72 patients and was negatively associated with HLA‐DQA1*0103‐B1*0603 (OR=0.12, P=0.015) and positively with DQA1*0501‐B1*0201 (OR=1.9, P=0.032). PCA‐positivity was linked to HLA‐DQA1*0501‐B1*0301 (OR=3.9, P=0.017). A link between H. pylori and PCA was observed when PCA‐positivity was defined as a titre ≥ 1/20 (OR=2.0, P=0.03), but not if ≥ 1/40 was the cut‐off point. PCA‐positivity, but not H. pylori infection, was associated with iron deficiency anaemia (OR=2.7, P=0.008), pernicious anaemia (OR= 33.5, P < 0.0001), hypochlorhydria (OR=12.1, P=0.0008) and autoimmune gastritis (OR=12.5, P < 0.0001). Conclusions: The HLA‐bound susceptibility of H. pylori and PCA differed. PCA‐positivity but not ongoing H. pylori infection is associated with autoimmune gastritis. Low titres of PCA might reflect H. pylori infection rather than autoimmune gastropathy.

Gastric Parietal Cell Antibodies, Helicobacter Pylori Infection, and Chronic Atrophic Gastritis: Evidence from a Large Population-based Study in Germany

“…For example, APCA appeared during 32 years of follow-up in a subject who was H. pylori negative at both baseline and final examination (25), and studies conducted in childhood populations failed to detect H. pylori infection for some children with APCA (15,26,27). In addition, APCA and H. pylori infection have been suggested to be associated with different HLA-DQ haplotypes in patients with type I diabetes (28). In another study, APCA antibodies did not decrease after cure of H. pylori infection over 1 year for a portion of patients (29).…”

Autoimmune Gastropathy in Type 1 Diabetic Patients With Parietal Cell Antibodies

“…Models for the pathogenesis of HP-associated autoimmunity are molecular mimicry and/or T-helper 1-induced expression of HLA class II and costimulatory molecules on gastric epithelial cells (24 -26). However, we and others (35,46,47) have found no or a negative relation between HP infection and autoimmune gastritis. Nevertheless, eradicating HP and doing a rebiopsy 6 months later to note its effect on histology is recommended.…”

“…13 C Urea breath tests were performed as previously described (34). Antrum, corpus, and fundus biopsies were examined for HP colonization using modified Giemsa and/or immunostaining (35). HP infection was diagnosed if any test was positive.…”

“…Islet cell antibodies (ICAs, normal level Ͻ12 Juvenile Diabetes Foundation units) were determined by indirect immunofluorescence on cryosections of human donor pancreas, GAD-65 antibodies (GADAs) (normal level Ͻ2.6% tracer bound), and tyrosine phosphatase (IA2 antigen, normal level Ͻ0.5% tracer bound) by liquid-phase radiobinding assay using Centricon-purified recombinant human 35 S-GAD65 and the 35 Slabeled intracellular domain of IA2 as tracer (32), respectively. PCAs were detected using indirect immunofluorescence on rat gastric mucosa (Medical Diagnostics California, Carlsbad, CA) (normal level Ͻ1/20 dilution) (3).…”

“…Gastric acid secretion studies were performed in 42 patients (15 PCA ϩ and 27 PCA -) after a 12-h overnight fast using pentagastrin-stimulated acid output (6 g/kg s.c. Pentagastrin Injection BP; Cambridge Laboratories, Newcastle upon Tyne, U.K.) (35). Hypochlorhydria was defined as a maximal acid output Ͻ15 mmol H ϩ /h.…”