Elucidation of pathophysiology and development of treatment for IgG4-related disease (RD)

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15290
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: CHIBA Tsutomu 京都大学, 医学研究科, 名誉教授 (30188487)
• Research Collaborator: SEKIGUCHI Kiyotoshi ; SHIOKAWA Masahiro ; KURIYAMA Katsutoshi
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: IgG4関連疾患 / 自己免疫性膵炎 / 自己抗体 / IgG / IgG4 / Extracellular matrix

Outline of Final Research Achievements

According to the hypothesis that IgG4-related disease (RD) is an autoimmune disease, we tried to clarify the existence of and roles for autoantibodies in patients with IgG4-RD. We first confirmed that injection of IgG in the sera of patients with IgG4-RD induced autoimmune pancreatitis (AIP)-like lesions in mouse pancreas. We also observed that the injected IgG was localized in extracellular matrix (ECM) including basement membrane of pancreatic acini together with C1q, suggesting that the autoantibody in patients’ serum recognizes some ECM protein in the pancreas. Thus, we established ELISA for various laminins, and found that about 50% of the patients with IgG4-RD had antibody against laminin α5β1γ1 -E8 in their sera, but none of normal subjects, patients with pancreatic cancer or those with chronic pancreatitis had this antibody. We concluded this antibody has pathogenic role by dissociating acinar cells from ECM.

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