中国系统性硬化症患者硬皮病相关自身抗体的检测及其临床意义

The detection of scleroderma-related autoantibodies and its clinical significance in 135 Chinese patients with systemic sclerosis

目的检测中国系统性硬化症（SSc）患者血清中硬皮病相关自身抗体一抗Sel-70抗体、抗着丝点抗体（ACA）和抗RNA多聚酶Ⅲ抗体（ARA），分析其与各种临床表现之间的关系。方法序贯纳入人选欧洲抗风湿病联盟硬皮病实验研究组（EULAR Scleroderma Trial and Research Group，EUSTAR）的135例中国SSc患者，分别用线性免疫印迹法、免疫双扩散法和间接免疫荧光法检测ARA、抗Scl-70抗体、ACA在患者血清中表达水平，并进一步分析自身抗体与患者各种临床表现之间的相关性。结果在135例SSc患者中抗Sel-70、ACA、ARA的阳性率分别为49．6％、13．3％和8．9％。抗Scl-70抗体阳性组患者的病程显著短于阴性组[（71±59）个月VS（90±103）个月，P=0．041]，肺间质病变的患炳率亦显著高于阴性组（P=0．031），但阳性组肺动脉高压的患病率显著低于阴性组（P=0．042），修订的Rodnan皮肤硬化评分（P=0．008）、面颈部皮肤硬化（P=0．002）、肘／膝关节远端皮肤硬化（P=0．004）以及指端凹陷性瘢痕／指垫消失的发生率（P=0．01）均显著高于阴性组；ACA阳性组患者的病程长于阴性组，差异具有统计学意义[（90±107）个月VS（69±64）个月，P=0．036]，肺间质病变的患病率显著低于阴性组（P＝0．045），IgM水平亦显著低于阴性组（P=0．045）；ARA阳性组和阴性组患者的病程等各项临床指标差异均无统计学意义，但阳性组血清肌酐和尿素氮水平显著高于阴性组（P〈0．001）。ACA和ARA患者各项皮肤硬化指标在阳性组和阴性组差异均无统计学意义。结论硬皮病特异相关的自身抗体与不同的临床表现紧密相关，检测此类抗体可能有助于SSc的诊断、脏器受累和预后评估。这些自身抗体在中国SSc患者的临床相关性可能不同于其他地区的SSc患者。

Objective To detect the expression of scleroderma-related autoantibodies, such as anti-Scl-70, anti-centromere antibody （ACA）and anti-RNA polymerase III （ARA）, and their relationship with clinical features in Chinese systemic sclerosis （SSc） patients. Methods One hundred and thirty-five Chinese SSc patients from the clinical database of the Scleroderma Trials and Research Group proposed by European League Against Rheumatism＇s Scheroderma Trial and Research Group （EUSTAR） were consecutively enrolled. The expression of ARA, anti-Scl-70 and ACA were detected through linear immunoblotting, double immunodiffusion and indirect immunofluorescence, respectively. The relevance between the existing of autoantibodies and clinical manifestations was analyzed statistically. Results Among the 135 Chinese SSc patients, the prevalence of anti-Scl-70, ACA, ARA were 49.6% , 13.3 % and 8.9% respectively. Patients with anti-Scl-70 antibody had significantly shorter disease course [ （71 ± 59） month vs （90 ±103） month, P = 0.041 ], higher proportion of interstitial lung disease （ P = 0.031 ） but lower of pulmonary arterial hypertension （P =0.042）. Modified Rodnan＇s skin score （P =0. 008） and prevalence of facial and cervical cutaneous sclerosis（P =0.002）, distal （to elbow/knee） cutaneous sclerosis （P = 0. 004）and digital pitting scarring/disappear of digital pad were all significantly higher in anti-Scl-70 positive group. Patients with ACA had longer disease course （ P = 0. 036） , lower IgM level （ P = 0. 045 ） and were less prevalent of interstitial lung disease （P = 0. 045 ）. Patients with ARA had higher serum creatinine and urea nitrogen level （P 〈0.001） although otherwise features had unremarkable differences. Conclusion Scleroderma-related autoantibodies have relevance with different clinical manifestation and detection of these autoantibodies may be helpful to the diagnosis of SSc, organ involvement evaluation and predicting outcomes. The clinical relevances of autoantibodies in Chinese SSc patients may differ from other areas or races.