Single cell analysis of B cells of patients with systemic sclerosis and mouse models of systemic sclerosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22919
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0903:Organ-based internal medicine and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Ebata Satoshi 東京大学, 医学部附属病院, 助教 (80884569)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: B細胞

Outline of Final Research Achievements

In patients and mouse models of systemic scleroderma (SSc), many B cells adhered to vascular endothelial cells in a microvascular model. Single-cell analysis of these B cells by micro-ELISA revealed a high percentage of autoreactive B cells producing anti-vascular endothelial cell antibodies and anti-topoisomerase I antibodies.
This subpopulation of autoreactive B cells was divided into those with strong adhesion to vascular endothelial cells (strongly adherent B cells) and those with weak adhesion (weakly adherent B cells), and strongly adherent B cells were found to be increased in patients with severe SSc and in mouse models of severe SSc. Weakly adherent B cells were more likely to produce IL-10, an anti-inflammatory cytokine, while strongly adherent B cells were more likely to produce IL-6, an inflammatory cytokine.

Free Research Field

膠原病

Academic Significance and Societal Importance of the Research Achievements

全身性強皮症は、予後不良な自己免疫疾患であり、難病に指定されている。2021年に新規の治療薬としてリツキシマブが保険承認されたが全ての患者に等しく有効というわけではなく、リツキシマブに対して治療抵抗性を示す患者がいるメカニズムは解明されていなかった。
本研究では、単一細胞解析の技術を用いることで、重症の全身性強皮症の病態形成において、炎症性サイトカインを産生する一部の自己応答性B細胞が重要な役割を果たしていることが示唆された。この研究成果は、リツキシマブに対する治療効果が乏しい全身性強皮症患者がいる理由の解明や、より効果的な治療薬を開発するための大きな助けになると考えられる。