冠動脈疾患に苦しむ個人の白血球サブセット上の補体調節タンパク質CD35、CD46、CD55、およびCD59の変化した発現

Altered Expression of Complement Regulatory Proteins CD35, CD46, CD55, and CD59 on Leukocyte Subsets in Individuals Suffering From Coronary Artery Disease.

• Nitesh Mishra
• Madhav Mohata
• Rajeev Narang
• R Lakshmy
• Anjali Hazarika
• R M Pandey
• Nibhriti Das
• Kalpana Luthra

抄録

動物モデルで行われた研究では、膜補体調節タンパク質が冠動脈疾患（CAD）の病態生理に重要な役割を果たしていることが示唆されている。本研究では、安定したCADを有する100名の個人と、男性を主な対象とする100名の健常対照者をリクルートした。補体調節タンパク質（Cregs）CD35、CD46、CD55、CD59の血漿中濃度と顆粒球、リンパ球、単球上での表面発現をフローサイトメトリーで評価した。これらのCregsの全白血球におけるmRNA発現を定量PCR法で測定した。Cregs の可溶性形態、C3c、Mannose binding protein-associated serine protease 2 (MASP-2)、Platelet activating factor-acetyl hydrolase (PAF-AH)、および炎症性サイトカインを ELISA により定量した。CAD患者では、補体活性化を示すC3cの血漿中濃度が高く、Cregsの血漿中濃度が有意に低かった。CAD患者では、リンパ球、単球、顆粒球の表面におけるCD46とCD55の発現が健常者と比較して有意に低く、顆粒球の表面におけるCD35とCD59の発現が高かった（<0.0001）。顆粒球上でのCD59の高発現は疾患の重症度と正の相関があり、CADにおける疾患進行の潜在的なマーカーとなる可能性がある。

Studies conducted in animal models have suggested that membrane complement regulatory proteins play an important role in the pathophysiology of coronary artery disease (CAD). In this study, a total of 100 individuals, with stable CAD and 100 healthy controls, both groups predominantly male, were recruited. We evaluated the plasma levels of complement regulatory proteins (Cregs) CD35, CD46, CD55, and CD59 and their surface expression on granulocytes, lymphocytes, and monocytes by flow cytometry. The mRNA expression of these Cregs in total leukocytes was determined by quantitative PCR. The soluble forms of Cregs, C3c, Mannose binding protein-associated serine protease 2 (MASP-2), Platelet activating factor-acetyl hydrolase (PAF-AH), and inflammatory cytokines were quantified by ELISA. High plasma levels of C3c, indicative of complement activation, in addition to significantly low levels of Cregs, were observed in CAD patients. A significantly lower expression of CD46 and CD55 on the surface of lymphocytes, monocytes, and granulocytes and higher surface expression of CD35 and CD59 on granulocytes ( < 0.0001) was seen in CAD patients as compared to healthy donors. The high expression of CD59 on granulocytes positively correlated with the severity of disease and may serve as a potential marker of disease progression in CAD.