Karasawa Rie, Fujieda Mikiya, Yudoh Kazuo
Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
Nihon Rinsho Meneki Gakkai Kaishi. 2010;33(4):207-13. doi: 10.2177/jsci.33.207.
Anti-endothelial cell antibodies (AECA) were antibodies targeting the antigens expressed on the endothelial cell surface. It has been reported that AECA were detected frequently in patients with vasculitis and were associated with disease activity and vasculitis symptoms. Consequently, AECA are thought to be involved in pathophysiology of vasculitis, including Kawasaki disease (KD); however, the role of AECA is not clear yet. One of the causes is that target proteins of AECA have been poorly identified. Therefore, we try to detect new target proteins of AECA in patients with vasculitis using proteomics. We have identified 63 proteins out of about 150 endothelial cell-specific candidate target proteins of AECA in patients with vasculitis so far. One of the identified proteins was peroxiredoxin2 (Prx2), an antioxidant enzyme. Our research suggests that the anti-Prx2 antibodies are detected frequently in patients with vasculitis and may have pathogenic roles in vasculitis via inflammatory cytokines/chemokines production and inhibition of anti-oxidative activity of Prx2. In this paper, we overview our study of the autoantigens detected by AECA in patients with vasculitis, and will provide some data on clinical significance of autoantibodies to Prx2, a target protein of AECA, in patients with KD.
抗内皮细胞抗体(AECA)是针对在内皮细胞表面表达的抗原的抗体。据报道,AECA在血管炎患者中经常被检测到,并且与疾病活动和血管炎症状相关。因此,AECA被认为参与了包括川崎病(KD)在内的血管炎的病理生理学过程;然而,AECA的作用尚不清楚。原因之一是AECA的靶蛋白尚未得到很好的鉴定。因此,我们尝试使用蛋白质组学方法在血管炎患者中检测AECA的新靶蛋白。到目前为止,我们已经在血管炎患者中鉴定出了约150种AECA内皮细胞特异性候选靶蛋白中的63种蛋白。其中一种被鉴定出的蛋白是过氧化物酶2(Prx2),一种抗氧化酶。我们的研究表明,抗Prx2抗体在血管炎患者中经常被检测到,并且可能通过炎症细胞因子/趋化因子的产生以及抑制Prx2的抗氧化活性在血管炎中发挥致病作用。在本文中,我们概述了我们对血管炎患者中AECA检测到的自身抗原的研究,并将提供一些关于AECA的靶蛋白Prx2自身抗体在KD患者中的临床意义的数据。