The important roles of a common protective allele HLA-DRB1*13:02 in collagen diseases.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08402
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Tokyo National Hospital (Clinical research) (2019-2020); University of Tsukuba (2018)
• Principal Investigator: Hiroshi Furukawa 独立行政法人国立病院機構東京病院(臨床研究部), 臨床研究部, 臨床研究部長 (00372293)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 病因・病態 / HLA / 遺伝子解析

Outline of Final Research Achievements

DRB1*13:02 allele is protective against systemic autoimmune diseases including systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). The protective effect of DRB1*13:02 was investigated in mixed connective tissue disease and polymyalgia rheumatica. DRB1*13:02 was protective against mixed connective tissue disease and DR6 (DRB1*13, DRB1*14) serological group was protective against polymyalgia rheumatica.
Transgenic mouse of DRB1*13:02 was generated in MRL/Mp.Faslpr and C57BL/6. The protein of DRB1*13:02 was confirmed in C57BL/6, but not in MRL/Mp.Faslpr. Pristane-induced lupus model was developed in transgenic mouse of DRB1*13:02 in C57BL/6. However, al the mice were dead before the evaluation.

Free Research Field

膠原病・アレルギー内科学

Academic Significance and Societal Importance of the Research Achievements

HLAのアレルHLA-DRB1*13:02が膠原病やその類縁疾患の発症に共通して抑制的に関連することを、日本人集団での関連解析で明らかにしてきた。この研究では、MCTDの発症にDRB1*13:02 は負の関連を示し、PMRの発症にDR6(DRB1*13, DRB1*14)は負の関連を示し、この関連は確かなものと考えられた。DRB1*13:02トランスジェニックマウスを作成し、DR13分子が膠原病発症を抑制する可能性を検証しようとしたが、叶わなかった。DR13分子が膠原病の発症を抑制する機序を明らかにすることはできなかった。