Study of the association between anti-DNA antibodies and HLA class II in systemic lupus erythematosus

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16285
• 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: Kyoto University
• Principal Investigator: Tsuji Hideaki 京都大学, 医学研究科, 助教 (50894755)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 全身性エリテマトーデス

Outline of Final Research Achievements

The aim of this study is to analyze the function of HLA class II molecules involved in systemic lupus erythematosus and to elucidate the mechanism of anti-DNA antibody production. When cells expressing HLA class II molecules were co-cultured with genomic DNA, specific binding of DNA to HLA-DR on the cell surface was observed. The binding ability of DNA to each allele of HLA class II molecules was associated with disease susceptibility to SLE. DNA-responsive BCR-expressing reporter cells were activated by DNA presented by HLA class II molecules. Immunization of mice with DNA/HLA class II molecule complexes did not stimulate nephritis or production of anti-DNA antibodies.

Free Research Field

膠原病

Academic Significance and Societal Importance of the Research Achievements

HLAクラスII分子とDNAの結合性、およびその疾患感受性との関連、HLAクラスII分子/DNA複合体によるB細胞受容体の反応性が解明された。抗DNA抗体は疾患活動性と相関し、SLEの発症に関わる重要な自己抗体であることより、本研究成果はSLEの病態解明につながると考えられる。さらに今後、抗DNA抗体産生の制御によるSLEの新規治療法の創出が期待できる。