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.

Journal article

Background and objectives

Helicobacter 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.

Methods

Clinical 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.

Results

85% 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 IgG4þ plasma-cell count (<10/HPF; range 1e4/ HPF), and duodenal specimens had an increased IgG4 count (>10/HPF; range 7e54) 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.

Conclusions

In 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 abstract: Peptic ulceration, Antigens, B cells, T cells, Interleukins, Helicobacter pylori.

Authors: Culver, E; Smit, W; Evans, C; Sadler, R; Cargill, T

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Pancreatology
• Volume: 17
• Issue: 3
• Pages: 395-402
• Publication date: 2017-04-01
• Acceptance date: 2017-04-04
• DOI: 10.1016/j.pan.2017.04.002
• EISSN: 1424-3911
• ISSN: 1424-3903
• Language: English
• Keywords: IgG4; IgG4-related disease; Adaptive immunity; Helicobacter pylori; Autoimmune pancreatitis