The role of autoimmunity in the pathogenesis of thrombocytopenia associated with hepatitis C

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kitasato University
• Principal Investigator: Satoh Takashi 北里大学, 医療衛生学部, 講師 (90407114)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 血小板減少 / 自己免疫 / C型慢性肝炎 / 抗GPIIb/IIIa抗体産生B細胞 / BAFF

Outline of Final Research Achievements

The pathogenesis of thrombocytopenia in chronic hepatitis C (CHC) conceivably involves autoimmunity; however, the dynamics of autoantibodies and other autoimmune mechanisms remain unclear. In this study, we examined the changes in the frequency of anti-glycoprotein (GP) IIb/IIIa antibody-producing B cells and the levels of plasma cytokines following treatment of CHC with direct-acting antiviral agents (DAA). Platelet counts increased significantly, and the frequency of anti-GPIIb/IIIa antibody-producing B cells decreased significantly in CHC patietnts with thrombocytopenia at the end of treatment (EOT) than before DAA treatment (baseline). However, these changes were not observed in CHC patients without thrombocytopenia. Plasma BAFF levels in CHC patients with thrombocytopenia significantly decreased from baseline to EOT. These results suggest that DAA treatment suppresses the autoimmune response against platelets and improves thrombocytopenia.

Free Research Field

血液検査学

Academic Significance and Societal Importance of the Research Achievements

肝疾患に伴った血小板減少の病態を正確に把握し、それに基づいた検査法の開発や治療法の選択が強く求められる。本研究の知見において、抗GPIIb/IIIa抗体産生B細胞数や血漿BAFF濃度を経時的に測定することは、治療効果判定などに有効であると考えられる。
また、C型慢性肝炎は肝臓以外の臓器及び組織に多彩な病変を合併することが知られ、これらを肝外病変と総称されている。肝外病変の原因としては、HCV感染に対する免疫異常および病変部へのHCV感染の関与が考えられて、病態として自己免疫疾患も存在する。本研究は自己免疫が関与する肝疾患の病態解明にも繋がると期待される。