Development of diagnosis methods for autoimmune dyslipidemia

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Osaka University
• Principal Investigator: YAMAMOTO Hiroyasu 大阪大学, 医学系研究科, 准教授 (00631201)
• Co-Investigator(Kenkyū-buntansha): 木原 進士 大阪大学, 医学系研究科, 教授 (20332736)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 自己免疫性脂質異常症 / 自己抗体 / アポリポ蛋白 / GPIHBP1 / リポ蛋白リパーゼ

Outline of Final Research Achievements

Autoantibodies against lipid metabolism-related molecules were investigated in the undiagnosed dyslipidemic patients with whom we were consulted by medical institutions nationwide. Among them, we identified two cases of hypertriglyceridemia induced by the autoantibodies against either apoC-II or GPIHBP1.
We also determined the clinical significance of anti-apoB-100 autoantibodies. First, we found that the serum anti-apoB-100 autoantibody levels were significantly low in diabetic patients with macroangiopathy comparing to those without. No clear association was found between serum anti-apoB-100 autoantibody levels and diabetic microangiopathy. Second, serum anti-apoB-100 autoantibody levels were positively correlated with plaque stability of culprit coronary vessels in male patients with stable angina. These results suggest that anti-apoB-100 autoantibodies would be a negative marker for the onset and progression of arteriosclerosis.

Free Research Field

内分泌・代謝内科学, 臨床検査医学

Academic Significance and Societal Importance of the Research Achievements

我々の研究をもとに自己免疫性脂質異常症が2015年に本邦の指定難病「原発性高カイロミクロン血症」の原因の１つに追記されたが、診断法が確立しておらず、臨床の実態は明らかではない。今回の研究では診断に難渋していた患者の確定診断に寄与できた。さらに、脂質代謝に関わる分子のうち、LDL-コレステロールの代謝に関わるアポ蛋白B-100の自己抗体価が、大血管障害をもつ糖尿病患者では低値であること、男性安定狭心症患者の責任冠動脈のプラークが安定しているものでは高値であることを見出した。従って、抗apoB-100自己抗体は動脈硬化症の発症・進展と関連し、患者の予後判定のマーカーとなる可能性を示した。