Investigation on mechanism for expansion of GM-CSF autoantibody by next generation sequencing.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390208
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Niigata University
• Principal Investigator: NAKATA Koh 新潟大学, 医歯学総合病院, 教授 (80207802)
• Co-Investigator(Kenkyū-buntansha): TAZAWA Ryushi 新潟大学, 医歯学総合病院, 准教授 (70301041) ; NAKAGAKI Kazuhide 日本獣医生命科学大学, 獣医学部, 准教授 (90143635) ; INOUE Yoshikazu 近畿中央胸部疾患センター, 臨床研究センター, センター長 (90240895) ; NEI Takahito 日本医科大学, 医学部, 助教 (30597670) ; TAKIZAWA Jun 新潟大学, 医歯学総合病院, 准教授 (70463990) ; YOKOSAKI Yasuyuki 広島大学, 保健センター, 准教授 (80210607)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肺胞蛋白症 / 自己免疫疾患 / 肺胞マクロファージ / 自己抗体 / 次世代シークエンス / バイオインフォーマティクス / クラススイッチ / 体細胞超変異

Outline of Final Research Achievements

It remains unclear why GM-CSF autoantibody is excessively produced in the patients. By preliminary evaluation using blood lymphocytes obtained from the patients and healthy subjects, we found high affinity IgG type GM-CSF autoantibody producing B cells expanded only in the patients but not in the healthy subjects, although IgM type producing B cells were even between them. It is suggested that class switching and clonal expansion are proceeding in the peripheral lymphnodes in the patients. To elucidate this, we tried to analyze the amino acid sequences of heavy chain variable regions using the next generation sequencing and a bioinformatics tool. Our analysis revealed that CDR1,2,and 3 amino acid sequences were variable and even in IgM clones but some specific sequences were exclusively used in IgG-type clones, suggesting oligo clonal expansion of IgG-type GM-CSF autoantibody clones in the patients.

Free Research Field

呼吸器内科学