Elucidation of pathological mechanisms for an autoantibody and development of therapy for autoimmune diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07393
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Chubu University
• Principal Investigator: Ohmi Yuhsuke 中部大学, 生命健康科学部, 助教 (10584758)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: シアル酸 / IgG / 自己免疫疾患 / st6gal1

Outline of Final Research Achievements

To identify the autoantibody ACPA produced in RA patients, we identified DNA sequence of the variable region in human ACPA and generated human monoclonal ACPA. To generate glycosylation-modified IgG, we produced St6gal1/B4galt1 gene-expressing CHO/dhfr- cell lines. We also generated Tg mice in which the St6gal1 gene or B4galt1 gene is specifically expressed in activated B cells.
In anti-glomerular basement membrane nephritis, we investigated whether sialylated anti-GBM antibodies can suppress pathological conditions. In the results, there was no significant difference in the onset level of anti-glomerular basement membrane nephritis between sialylated anti-GBM antibodies and anti-GBM antibodies. This suggests the existence of autoimmune diseases in which the anti-inflammatory reaction by sialylated autoantibodies is not effective.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患は自身の免疫異常によって惹起されるが、その制御メカニズムはまだ不明な点が多く、主な治療も対症療法になる。本研究では自己免疫疾患で認められる自身の身体に反応して傷害を誘導する自己抗体に注目した。特に関節リウマチなどに発現する自己抗体を同定し、さらに自己抗体上に発現している糖鎖構造による炎症制御について検討するためのマウスや抗体を作製した。これによって自己免疫疾患の制御メカニズムの一端が明らかにすることができる。