Metabolomic analysis in IgG4-related disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09511
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kanazawa Medical University
• Principal Investigator: IWAO Haruka 金沢医科大学, 医学部, 助教 (10612244)
• Co-Investigator(Kenkyū-buntansha): 河南 崇典 金沢医科大学, 医学部, 講師 (20350762) ; 正木 康史 金沢医科大学, 医学部, 教授 (40238895)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: IgG4関連疾患 / メタボロミクス / 脂質メディエーター

Outline of Final Research Achievements

IgG4-related disease is indicated by increased infiltration of IgG4-positive plasma cells, typically elevated IgG4 serum levels and the formation of lymphoplasmacytic infiltrate in one or more organs. We explored the metabolome of >400 small molecules in serum from 10 matched pair IgG4-related disease subjects prior to (PRE) and following (POST) steroid treatment and contrast these profiles with a cohort of 10 normal non-diseased subjects (NORM). The polyunsaturated fatty acid arachidonate is involved in pro-inflammatory activities through its metabolism to the pro-inflammatory prostaglandins via cyclooxygenase activity and HETEs via lipoxygenases. Individuals with PRE IgG4-related disease had elevated arachidonate and the 12-lipoxygenase product, 12-HETE, as compared to NORM subjects. The higher levels of the pro-inflammatory arachidonate and 12-HETE was unaffected by steroid treatment as POST subjects had similar levels of these biochemicals as was observed in PRE subjects.

Free Research Field

膠原病学、血液学

Academic Significance and Societal Importance of the Research Achievements

脂質メディエーターは極めて微量であること、半減期が短いこと、直接遺伝子にコードされないことなどから、横断的・総論的な研究はなされていなかった。本研究では、IgG4関連疾患の慢性炎症、炎症の遷延化に果たす脂質メディエーターに着目し、解析を行った。本研究で得られた知識は、IgG4関連疾患という一病変の解明だけに留まらず、炎症・代謝疾患に果たす、脂質メディエーターの制御の解析にも繋がると思われる。