The role of TRIM21 in B cell Abnormalities with Systemic Lupus Erythematosus

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23847
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Yokohama City University
• Principal Investigator: KUNISHITA Yosuke 横浜市立大学, 医学研究科, 客員研究員 (30849972)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: TRIM21 / 全身性エリテマトーデス / 抗TRIM21抗体 / B細胞 / 抗体産生 / Ⅰ型インターフェロン

Outline of Final Research Achievements

TRIM21 is a member of the tripartite motif family proteins and is one of the autoantigens which react with anti-SS-A antibody (Ab) present in sera of patients with systemic lupus erythematosus (SLE) and Sjogren's syndrome. Previous studies have shown that TRIM21 dysfunction promotes aberrant B-cell differentiation and Ab production in SLE, and anti-TRIM21 Ab may be related to the TRIM21 dysfunction in human SLE pathogenesis. In this study, we examined the relationship between anti-TRIM21 Ab and clinical and immunological characteristics in SLE patients. The serum levels of interferon (IFN)-β were significantly higher in patients with anti-TRIM21 Ab as compared with those without. The levels of IgG1 and IgA were significantly higher in SLE patients with anti-TRIM21 Ab as compared with those without. The PBMCs of patients with anti-TRIM21 Ab showed a significantly higher expression of TRIM21 protein as compared with those without.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

炎症性サイトカインや免疫グロブリンの血清レベル、TRIM21の発現は、治療介入によって変化する可能性があり、先行研究の知見を正確に検証するために、本研究は、SLEの治療前の血清と細胞を用いて行っており、非常に有意義なものとなった。本研究によって、抗TRIM21抗体はSLEにおけるI型インターフェロンの過剰産生とB細胞の過剰活性化に関連しており、その原因として、TRIM21の機能障害が存在する可能性が示唆された。抗TRIM21抗体は、SLEの病態において、Ⅰ型インターフェロンの過剰産生やB細胞の活性化により依存しているSLE患者の治療標的や新規バイオマーカーとなる可能性が示唆された。