Kodera Masanari, Hayakawa Ikuko, Komura Kazuhiro, Yanaba Koichi, Hasegawa Minoru, Takehara Kazuhiko, Sato Shinichi
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
J Rheumatol. 2005 Apr;32(4):629-36.
The vascular damage systemic sclerosis (SSc) consists mainly of microvascular changes, but recently macrovascular changes with dyslipidemia were recognized. In systemic lupus erythematosus (SLE), autoantibody to lipoprotein lipase (LPL), a key enzyme that hydrolyzes triglycerides, suggested a role of autoimmunity for elevated serum triglyceride levels and atherosclerosis. We investigated the prevalence and levels of anti-LPL antibodies, their clinical correlation, and their functional significance in patients with SSc.
Serum samples from patients with diffuse cutaneous SSc (dSSc; n = 55), limited cutaneous SSc (lSSc; n = 75), SLE (n = 21), and dermatomyositis (DM; n = 21) and healthy controls (n = 41) were examined by ELISA. The presence of anti-LPL antibody was evaluated by immunoblotting analysis using purified LPL. To determine the functional relevance of anti-LPL antibody in vivo, we assessed whether anti-LPL autoantibody was able to inhibit LPL activity using the LPL activity kit.
ELISA revealed that IgG or IgM anti-LPL antibodies were detected in 35% of SSc patients, while they were also positive in 67% of SLE patients and 43% of DM patients. The presence of IgG anti-LPL antibody was associated with elevated serum triglyceride levels, greater extent of skin fibrosis, and more frequent presence of lung fibrosis, heart involvement, and anti-topoisomerase I antibodies. The presence of anti-LPL autoantibody was confirmed by immunoblotting analysis. LPL activity was inhibited by IgG anti-LPL antibodies in sera from SSc patients with elevated serum triglyceride levels.
Our results suggest that anti-LPL autoantibody contributes to elevated serum triglyceride levels by inhibiting LPL enzyme activity in patients with SSc.
系统性硬化症（SSc）中的血管损伤主要由微血管变化构成，但最近伴有血脂异常的大血管变化也得到了确认。在系统性红斑狼疮（SLE）中，针对脂蛋白脂肪酶（LPL，一种水解甘油三酯的关键酶）的自身抗体提示自身免疫在血清甘油三酯水平升高和动脉粥样硬化中发挥作用。我们调查了SSc患者中抗LPL抗体的患病率、水平、它们的临床相关性及其功能意义。
通过酶联免疫吸附测定（ELISA）检测弥漫性皮肤型SSc（dSSc；n = 55）、局限性皮肤型SSc（lSSc；n = 75）、SLE（n = 21）、皮肌炎（DM；n = 21）患者以及健康对照者（n = 41）的血清样本。使用纯化的LPL通过免疫印迹分析评估抗LPL抗体的存在情况。为了确定抗LPL抗体在体内的功能相关性，我们使用LPL活性检测试剂盒评估抗LPL自身抗体是否能够抑制LPL活性。
ELISA显示，35%的SSc患者检测到IgG或IgM抗LPL抗体，而67%的SLE患者和43%的DM患者也呈阳性。IgG抗LPL抗体的存在与血清甘油三酯水平升高、皮肤纤维化程度加重以及肺纤维化、心脏受累和抗拓扑异构酶I抗体的出现更为频繁相关。通过免疫印迹分析证实了抗LPL自身抗体的存在。来自血清甘油三酯水平升高的SSc患者血清中的IgG抗LPL抗体抑制了LPL活性。
我们的结果表明，抗LPL自身抗体通过抑制SSc患者的LPL酶活性导致血清甘油三酯水平升高。
