Fillit H, Shibata S, Sasaki T, Spiera H, Kerr L D, Blake M
Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, NY, NY 10029-6574.
Autoimmunity. 1993;14(3):243-9. doi: 10.3109/08916939309077372.
Vascular heparan sulfate proteoglycan (vHSPG) has an important role in the normal vasculature, including hemostasis, lipolysis and other vascular functions. These functions are mediated by both the glycosaminoglycan and protein core moieties of vHSPG. Autoimmunity to vHSPG has been demonstrated to play a role in vascular injury in animal models, and is present in patients with autoimmune vascular disease. However, most previous studies of human autoimmunity to vHSPG have only investigated heparan sulfate glycosaminoglycan epitopes. In the current investigations, autoantibodies to the protein core of vHSPG in sera from patients with systemic lupus erythematosus (SLE) were investigated. vHSPG protein core was prepared by chemical deglycosylation. Competitive immunoinhibition ELISA and immunoblotting immunoassays were established employing monoclonal antibodies to vHSPG protein core. SLE sera were demonstrated to contain IgG autoantibodies reactive with the vHSPG protein core by immunoblotting. Human autoantibodies to vHSPG protein core were not inhibited by heparan sulfate confirming their protein core reactivity. Competitive immunoinhibition studies employing a solid phase radioimmunoassay also confirmed the reactivity of human sera with vHPSG protein core. By ELISA, a significant increase in the occurrence of anti-vHSPG protein core antibodies was noted in SLE sera. While most previous investigations have demonstrated autoimmunity to heparan sulfate, the presence of IgG autoantibodies to vHSPG protein core demonstrates that the entire vHSPG proteoglycan is the target of autoimmunity in SLE.
血管硫酸乙酰肝素蛋白聚糖（vHSPG）在正常血管系统中发挥着重要作用，包括止血、脂肪分解及其他血管功能。这些功能由vHSPG的糖胺聚糖和蛋白核心部分介导。在动物模型中，已证实针对vHSPG的自身免疫在血管损伤中起作用，且自身免疫性血管疾病患者体内也存在这种情况。然而，以往大多数关于人类对vHSPG自身免疫的研究仅调查了硫酸乙酰肝素糖胺聚糖表位。在当前研究中，对系统性红斑狼疮（SLE）患者血清中针对vHSPG蛋白核心的自身抗体进行了研究。通过化学去糖基化制备vHSPG蛋白核心。采用针对vHSPG蛋白核心的单克隆抗体建立了竞争性免疫抑制ELISA和免疫印迹免疫测定法。通过免疫印迹证明，SLE血清中含有与vHSPG蛋白核心反应的IgG自身抗体。硫酸乙酰肝素不会抑制人类针对vHSPG蛋白核心的自身抗体，证实了它们与蛋白核心的反应性。采用固相放射免疫测定法的竞争性免疫抑制研究也证实了人类血清与vHPSG蛋白核心的反应性。通过ELISA发现，SLE血清中抗vHSPG蛋白核心抗体的发生率显著增加。虽然以往大多数研究都证明了对硫酸乙酰肝素的自身免疫，但针对vHSPG蛋白核心的IgG自身抗体的存在表明，整个vHSPG蛋白聚糖是SLE自身免疫的靶标。
