Pathophysiology and targeted treatment of autoimmune hematological diseases based on the next generation high-throughput TCR/BCR repertoire analysis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08639
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Akita University
• Principal Investigator: Hirokawa Makoto 秋田大学, 医学(系)研究科(研究院), 教授 (50241667)
• Co-Investigator(Kenkyū-buntansha): 鈴木 隆二 独立行政法人国立病院機構(相模原病院臨床研究センター), 診断・治療研究室, 室長 (70373470) ; 藤島 直仁 秋田大学, 医学部, 講師 (70422152)
• Co-Investigator(Renkei-kenkyūsha): KITAURA Kazutaka 国立相模原病院, 診断治療研究室, 研究員 (00518136) ; MATSUTANI Takaji 国立相模原病院, 診断治療研究室, 研究員 (70372290)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 特発性血小板減少性紫斑病 / Bリンパ球 / B細胞抗原受容体 / レパトア / NGS

Outline of Final Research Achievements

To identify the pathological B-cell clones in primary ITP, we have investigated the repertoires of IgG-BCRs of peripheral blood B cells by using the high-throughput DNA sequencing. Unbiased amplifications of IgG-BCRs were performed by adaptor-ligation PCR. The amplicons were sequenced by next-generation sequencing. Comparisons of the IGHV repertoires covering fifty-nine IGHV subfamilies between the patients and controls revealed an increased usage of IGHV4-28 in ITP patients. The 186 distinct IGHV4-28-carrying sequences were identified in ITP patients and 135 out of these clones used the IGHJ4 gene segment. The present study has demonstrated the preferential usage of the rearranged IGHV4-28/IGHJ4 gene by circulating IgG B cells in ITP. Although the antigen specificity of BCRs encoded by the IGHV4-28/IGHJ4 gene in the present patient cohort remains to be elucidated, prolonged antigenic pressure appears to shape this characteristic BCR repertoire.

Free Research Field

内科学、血液内科学、免疫学