A potential biomaker with circulating auto-antibodies for cardiovascular disease in patients with obstructive sleep apnea

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09528
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Chiba University
• Principal Investigator: Terada Jiro 千葉大学, 医学部附属病院, 講師 (20400898)
• Co-Investigator(Kenkyū-buntansha): 日和佐 隆樹 千葉大学, 大学院医学研究院, 特任准教授 (30260251)
• Research Collaborator: Tatsumi Koichiro ; Matsumura Takuma
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 睡眠呼吸障害 / 動脈硬化 / 自己抗体 / バイオマーカー

Outline of Final Research Achievements

In the present study, we identified two autoantibodies as potential novel biomarkers of atherosclerosis. In the first study, we discovered that COPE-Ab levels were significantly higher in patients with OSA, particularly those with moderate to severe OSA. Furthermore, patients with OSA and also CVD and/or stroke, hypertension, and a high BMI had elevated levels of COPE-Ab. Second, an elevated COPE-Ab level was the significant predictor of a history of CVD and/or stroke in a multivariate analysis of patients with OSA. The major finding of the second study was that neuroblastoma1(NBL1)-Ab level was significantly elevated in patients with both OSA and ACS compared with HVs. Subgroup analyses showed that NBL1-Ab level was significantly higher in patients with severe OSA and OSA patients with a past history of CAD. According to our results, COPE-Ab and NBL1-Ab might therefore be a biomarker of the risk of cardiovascular and cerebrovascular events in patients with OSA.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究で示したような，閉塞性無呼吸症候群（OSA)患者の血清で同定できる特異的な心血管疾患マーカーが明らかになれば，臨床に直接関連する動脈硬化を簡便に評価できる検査となることが期待される．特に，どのようなOSA患者が数年～数十年後に脳梗塞、心筋梗塞が発症するリスクがあるかを定量的に予測することが可能となれば，本疾患の治療アルゴリズムに寄与する可能性が考えられる．近年，数多くのバイオマーカーが実臨床で用いられているが，抗体マーカーは，抗原マーカーや酵素マーカーと比較すると非常に安定した測定結果が得られることが特徴であるため，将来臨床応用が可能な非侵襲的な検査となることが期待される．