Investigation of the role of HLA-A in the pathogenesis of autoimmune vitiligo and regulatory mechanism of HLA-A expression

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10228
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Yamagata University
• Principal Investigator: HAYASHI MASAHIRO 山形大学, 医学部, 講師 (30396569)
• Co-Investigator(Kenkyū-buntansha): 鈴木 民夫 山形大学, 医学部, 教授 (30206502)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: HLA-A / 白斑 / 発症リスク / 一塩基多型 / eQTL

Outline of Final Research Achievements

Vitiligo is an autoimmune disease targeting skin melanocytes. The pathogenesis for vitiligo, including why the immune tolerance to melanocytes is broken or what the risk factor for vitiligo is, is still unclear. Previous study for Japanese patients with vitiligo revealed that the risk of vitiligo is associated with several single nucleotide polymorphisms (SNPs) located near HLA-A, which is closely associated with the immune response to melanocytes. In current study, the expression level of HLA-A mRNA of peripheral lymphocytes was higher in in patients with high risk SNP than without these SNPs (P=0.065). This finding suggests that higher level of HLA-A expression on the cell surface of lymphocyte facilitates the recognition of melanocyte related antigen, may lead to the disruption of immune tolerance and development of autoimmune response to to melanocytes.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

HLA-Aは免疫反応に関連する重要な分子の一つで、皮膚メラノサイトに対する自己免疫疾患である白斑において、細胞表面での自己抗原提示・認識に関与することで病態に重要な役割を果たしている。日本人白斑患者を対象にした以前の研究で、白斑の発症リスクに関係する一塩基多型（SNP）が、HLA-A近傍にあることが示された。本研究では、発症リスクの高まるSNPを持つ人では持たない人と比較して末梢血リンパ球のHLA-A mRNA発現が比較的高いことを示され、メラノサイト関連抗原がHLA-Aによって、より多く提示されることにより、免疫寛容の破綻と自己免疫反応の惹起につながることが示唆された。