The exploration of therapeutic target molecules for Sjogrens syndrome focusing on B cell subsets

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17916
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Keio University
• Principal Investigator: Takei Eriko 慶應義塾大学, 医学部(信濃町), 助教 (40594643)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: シェーグレン症候群 / B細胞 / 自己抗体

Outline of Final Research Achievements

The purpose of this study is to demonstrate the possible involvement of CD38highIgD+B cells in the pathogenesis of Sjogren’s syndrome (SS) by characterization of the cells from patients and autoimmune model mice, and consequently search novel therapeutic targets to treat SS. We found that expression levels of BAFF receptor (BR3) and IL-6 receptor were elevated in CD38highIgD+B cells of patients and that IgG production by SS B cells was enhanced upon the stimulation including BAFF as compared with healthy controls. In addition, proportion of CD38+IgD+ cells was decreased in splenocytes of MRL/lpr mice, autoimmune model mice, while the proportion of CD38+IgD- B cells and titer of anti-dsDNA antibody were increased with the progression of the disease. Our results indicate that CD38highIgD+ B cells highly react to BAFF and differentiate plasma cells to produce IgG and the pathways of differentiation of plasma cells from CD38highIgD+ B cells are promising therapeutic targets to treat SS.

Free Research Field

内科膠原病学　臨床免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究は指定難病であるシェーグレン症候群（SS）の病態の中心を担うB細胞の機能亢進について、CD38highIgD+B 細胞に焦点をおいてその機序を明らかにすることを目的としている。SSは、慢性唾液腺炎や乾燥性角結膜炎に加えて全身性に多彩な病態を合併し、患者のQOLは生涯に渡り著しく害されるが、病態形成のメカニズムが不明であるため病態に沿った根治薬は存在しない。本研究はB細胞の亜群に焦点を絞っており、基礎研究として極めて独創性、新規性が高く、研究成果は根治薬のない免疫難病領域に有効性の高い新規治療薬を提供するというアンメットメディカルニーズに応えることを可能とし、社会的な貢献度も高い。