Bodolay Edit, Prohászka Zoltan, Paragh Gyorgy, Csipő Istvan, Nagy Gabor, Laczik Renata, Demeter Nora, Zöld Eva, Nakken Britt, Szegedi Gyula, Szodoray Peter
Department of Clinical Immunology, Institute of Medicine, University of Debrecen Medical and Health Science Center, Debrecen, Hungary.
Immunol Res. 2014 Oct;60(1):50-9. doi: 10.1007/s12026-014-8552-x.
Heat-shock protein 60 (Hsp60) has been shown to provoke inflammation, and anti-Hsp60 may facilitate the development of atherosclerosis. In this study, we have investigated 30 patients with mixed connective tissue disease (MCTD) and assessed anti-Hsp60 and their relationship to cardiovascular diseases (CVD). Out of 30 patients with MCTD, 15 had CVDs. Anti-Hsp60 antibody was determined by enzyme-linked immunosorbent assay. Since endothelial dysfunction and accelerated atherosclerosis are characteristic to MCTD, a wide array of MCTD-, endothelial dysfunction- and CVD-associated parameters was investigated: serum lipid levels, paraoxonase activity (PON1), rich nuclear ribonucleoprotein U1 (anti-U1RNP), anti-endothelial cell antibodies, anti-cardiolipin and anti-β2-glycoprotein I antibody isotypes (anti-CL and anti-β2GPI), endothelin-1 (ET-1) levels, also intima-media thickness (IMT), a quantitative indicator of atherosclerosis. In MCTD, anti-Hsp60 antibody levels were significantly higher than in healthy individuals (p < 0.02). MCTD patients with CVD had significantly higher levels of anti-Hsp60 compared to MCTD without CVD (p = 0.001). Patients with MCTD had significantly lower high-density lipoprotein cholesterol (p = 0.02) and PON activity (p < 0.001), and significantly increased systolic (p < 0.0002) and diastolic (p < 0.001) blood pressure compared to healthy individuals. Anti-U1RNP levels (p < 0.002) and IMT were higher in patients compared to controls (p = 0.002). The CVD-positive MCTD patients had increased anti-Hsp60 (p < 0.0013), anti-CL IgG (p = 0.0005), ET-1 serum concentration (p < 0.05) and IMT levels (p < 0.001) compared to MCTD patients without CVD. Anti-Hsp60 showed a strong correlation with anti-oxLDL (r = 0.36, p = 0.01) and serum ET-1 (r = 0.62, p < 0.001) and negative correlation with PON activity (r = -0.47, p = 0.01). Anti-Hsp60 indicates endothelial injury, CVD, and can function as a novel atherosclerotic risk factor, also a valuable diagnostic marker in patients with MCTD.
热休克蛋白60（Hsp60）已被证明可引发炎症，而抗Hsp60可能会促进动脉粥样硬化的发展。在本研究中，我们调查了30例混合性结缔组织病（MCTD）患者，并评估了抗Hsp60及其与心血管疾病（CVD）的关系。在30例MCTD患者中，15例患有CVD。通过酶联免疫吸附测定法测定抗Hsp60抗体。由于内皮功能障碍和加速的动脉粥样硬化是MCTD的特征，因此研究了一系列与MCTD、内皮功能障碍和CVD相关的参数：血脂水平、对氧磷酶活性（PON1）、富核核糖核蛋白U1（抗U1RNP）、抗内皮细胞抗体、抗心磷脂和抗β2糖蛋白I抗体亚型（抗CL和抗β2GPI）、内皮素-1（ET-1）水平，以及内膜中层厚度（IMT），这是动脉粥样硬化的定量指标。在MCTD中，抗Hsp60抗体水平显著高于健康个体（p < 0.02）。患有CVD的MCTD患者的抗Hsp60水平显著高于未患CVD的MCTD患者（p = 0.001）。与健康个体相比，MCTD患者的高密度脂蛋白胆固醇显著降低（p = 0.02），PON活性显著降低（p < 0.001），收缩压（p < 0.0002）和舒张压（p < 0.001）显著升高。与对照组相比，患者的抗U1RNP水平（p < 0.002）和IMT更高（p = 0.002）。与未患CVD的MCTD患者相比，CVD阳性的MCTD患者的抗Hsp60（p < 0.0013）、抗CL IgG（p = 0.0005）、ET-1血清浓度（p < 0.05）和IMT水平（p < 0.001）升高。抗Hsp60与抗氧化低密度脂蛋白（r = 0.36，p = 0.01）和血清ET-1（r = 0.62，p < 0.001）呈强相关，与PON活性呈负相关（r = -0.47，p = 0.01）。抗Hsp60表明存在内皮损伤、CVD，可作为一种新的动脉粥样硬化危险因素，也是MCTD患者的一种有价值的诊断标志物。
