Clarification of pathophysiology of Takayasu Arteritis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860809
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyoto University
• Principal Investigator: TERAO Chikashi 京都大学, 医学(系)研究科(研究院), 助教 (60610459)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 自己免疫性疾患 / 高安動脈炎 / 全ゲノム関連解析

Outline of Final Research Achievements

We collected DNA samples and clinical information from more than 400 patients with Takayasu arteritis (TAK). We identified a novel susceptibility HLA-B allele and two novel non-HLA susceptibility loci. The top SNP in the IL12B region showed high odds ratio and was associated with complication and severity of aortic regurgitation, a severe complication of TAK. Furthermore, the SNP demonstrated a synergistic effect with HLA-B*52:01, the strongest HLA susceptibility allele to TAK. These results indicate that IL12p40, encoded by IL12B, is a key molecule to TAK. Furthermore, we showed that 6.4% of patients with TAK suffered from ulcerative colitis (UC), one of inflammatory bowel diseases (IBD). We also showed a significant genetic overlap between TAK and UC, suggesting that the two diseases share common molecular pathways. Furthermore, we showed that ustekinumab, a monoclonal antibody to IL12p40 used for patients with IBD, was effective to patients with TAK in a pilot clinical study.

Free Research Field

免疫ゲノム医学