Autoimmune Pancreatitis Associated With High Prevalence of Gastric Ulcer Independent of Helicobacter pylori Infection Status

Chang, Ming‐Chu; Chang, Yu-Ting; Wei, Shu–Chen; Kuo, Chun-Hung; Liang, Po-Chin; Wong, Jau‐Min

doi:10.1097/mpa.0b013e31819b5f3c

Cited by 22 publications

(9 citation statements)

References 23 publications

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“…The single gastric ulcer was found in the antrum and was non-linear, which was different to the distribution and morphology described at endoscopy in one AIP series [19]. H. pylori -associated gastritis was detected in 23.5% of patients with IgG4-RD, similar to the 20% described in a Chinese AIP cohort [22]. This H. pylori –associated chronic active gastritis was characterised by an infiltration of the gastric epithelium and lamina propria by B and T cells, plasma cells, neutrophils, macrophages and mast cells.…”

Section: Discussioncontrasting

confidence: 72%

“…Seroprevalence of anti - H. pylori IgG in our UK IgG4-RD cohort was 23.6%, which is comparable to Chinese AIP cohorts (27.5%), but considerably lower than the Italian AIP cohort (84%) from which H. pylori PBP reactivity was originally identified [13], [22]. This may be explained by an over-representation of type II AIP in the Italian cohort given that the percentage of patients with elevated serum IgG4 in this group was low (50%) compared to UK and Asian cohorts (82–95%).…”

Section: Discussionsupporting

confidence: 48%

“…Clinical history and endoscopic evidence of peptic ulceration was described in only 7.2% of patients with IgG4-RD, much lower compared to the 22.5 and 34.8% of gastric ulcers at endoscopy described in Chinese and Japanese AIP patients, respectively [10], [22]. These discrepancies may originate from regional differences in H. pylori colonisation and circulating strains causing ulceration, ethnicity-related susceptibility factors to both AIP and H. pylori infection, or that 17% of our IgG4-RD cohort did not have pancreatic and/or biliary disease [25].…”

Section: Discussionmentioning

confidence: 77%

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No evidence to support a role for Helicobacter pylori infection and plasminogen binding protein in autoimmune pancreatitis and IgG4-related disease in a UK cohort

et al. 2017

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Background and objectivesHelicobacter pylori (H.pylori) plasminogen binding protein (PBP) has been proposed as an antigen triggering autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease (IgG4-RD). We investigated exposure to H. pylori infection, cytokine response and immunological memory to H. pylori PBP in a prospective IgG4-RD cohort in the UK.MethodsClinical and endoscopic evidence of peptic ulceration, serological H. pylori exposure and serum IgG4 levels were obtained in 55 IgG4-RD patients and 52 disease controls (DC) with autoimmune or inflammatory conditions with an elevated serum IgG4. Gastric and duodenal tissues were assessed for H. pylori and immunostained for IgG4. B and T cell ELISpot and cytokine luminex assays were used to detect immune responses to H. pylori PBP.Results85% of IgG4-RD patients had pancreatic and/or biliary disease, 89% had extra-pancreatic manifestations, and 84% had an increased serum IgG4. Clinical dyspepsia (35.2%), gastritis (58%), peptic ulceration (7.4%) and H. pylori colonisation (24%) in IgG4-RD was similar to DC. In IgG4-RD, gastric tissue contained a chronic inflammatory infiltrate with a low IgG4+ plasma-cell count (<10/HPF; range 1–4/HPF), and duodenal specimens had an increased IgG4 count (>10/HPF; range 7–54) compared with DC (p < 0.01). Th1 and Th2 cytokine response and immunological B-cell memory to H. pylori PBP did not differ between IgG4-RD and DC.ConclusionsIn a prospective UK cohort, the prevalence of gastric ulceration, exposure to H. pylori, cytokine response and immunological memory to H. pylori PBP did not differ in IgG4-RD patients compared with DC. This study does not support a role for H. pylori PBP as a microbial antigen in IgG4-RD.Keywords for abstractPeptic ulceration, Antigens, B cells, T cells, Interleukins, Helicobacter pylori.

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Section: Discussioncontrasting

confidence: 72%

Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 77%

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No evidence to support a role for Helicobacter pylori infection and plasminogen binding protein in autoimmune pancreatitis and IgG4-related disease in a UK cohort

et al. 2017

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“…The disease may represent a hypersensitive/allergic reaction as compared to being an autoimmune disease 189. An association of IgG4-related AIP with gastric ulcer and Helicobacter pylori (H. pylori) infection has been proposed 190-192. It has been theorized by Okazaki, et al193 that the development of the acronym 'AIP' involves a biphasic mechanism in which the initial response to self-antigens such as carbonic anhydrase, lactoferrin, pancreatic secretory trypsin inhibitor and ά-fodrin and molecular mimicry (H. pylori) are induced by decreased naive regulatory T cells, in conjunction with T-helper 1 cells releasing proinflammatory cytokines.…”

Section: Proposed Etiopathogenesis Of Igg4-related Sclerosing Diseasementioning

confidence: 99%

IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

2012

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Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies.

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“…Two previous studies, from Japan and Taiwan, have identified an increased prevalence of gastric ulceration in patients with autoimmune pancreatitis and this appears to be independent of Helicobacter pylori infection status 6 7. In one of these studies, gastric biopsy material was obtained from some of the patients and this revealed prominence of IgG4-positive plasma cells within the gastric mucosa 6.…”

Section: Discussionmentioning

confidence: 95%

Chronic gastric ulceration: a novel manifestation of IgG4-related disease?

2012

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Autoimmune Pancreatitis Associated With High Prevalence of Gastric Ulcer Independent of Helicobacter pylori Infection Status

Abstract: Our results demonstrated that GU was more prevalent in AIP compared with nonautoimmune CP. Positive H. pylori status and host TNF-alpha promoter susceptibility could not explain the pathogenesis of higher GU prevalence and pathogenesis of AIP in our population.

Cited by 22 publications

References 23 publications

No evidence to support a role for Helicobacter pylori infection and plasminogen binding protein in autoimmune pancreatitis and IgG4-related disease in a UK cohort

No evidence to support a role for Helicobacter pylori infection and plasminogen binding protein in autoimmune pancreatitis and IgG4-related disease in a UK cohort

IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

Chronic gastric ulceration: a novel manifestation of IgG4-related disease?

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