异质性胞核核糖核蛋白I(hnRNP I)抗原表位在系统性硬化症中的临床研究

Clinical research of heterogeneous nuclear ribonucleoprotein (hnRNP) I in systemic sclerosis

目的探讨异质性核糖核蛋白I(hnRNPI)的抗原表位多肽在系统性硬化症(SSc)中的临床意义,初步建立简便快捷的ELISA检测方法,为系统性硬化症的早期诊断寻找新的临床指标。方法根据已知的hnRNPI蛋白氨基酸序列,应用不同的蛋白质抗原表位图谱分析软件对其进行表位分析,经比对筛选后,化学合成hnRNPI短肽序列2个,分别命名为hnRNPI-1(I-1)及hnRNPI-2(I-2),作为抗原,对321例包括硬皮病在内的多种结缔组织病患者血清相应抗体进行ELISA检测。结果抗hnRNPI-1及抗hnRNPI-2多肽抗体在SSc组中阳性率为43.4%及47.8%,均显著高于其他疾病组(P﹤0.05),在SSc中敏感性分别为43.4%及47.8%,特异性分别为88.6%及87.6%,二者之间均无显著性差异(P﹥0.05)。除与SSc患者病程相关外,该二抗体与发病年龄、临床症状、器官受累、血沉、抗Scl-70抗体及抗着丝点抗体之间均无显著性差异(P﹥0.05)。结论I-1及I-2分别是位于hnRNPI蛋白表面的抗原表位之一,具有抗原性,其抗体对SSc的临床诊断具有较高的敏感性及特异性,且在病程早期具有更高的阳性率,有助于SSc的早期诊断。

Objective To assess the presence of autoantibodies against the epitopes of hnRNP I in systemic sclerosis （SSc） as well as other CTDs. Methods Polypeptides of hnRNP I were designed based on the animo acids sequence by the biologic technical software. The sera from different patients including 113 SSc, 45 SLE, 37 SS, 20 MCTD, 50 RA, 28 SPA, 30 other diffused rheumatic diseases, and 54 controls were detected by ELISA with the synthetic polypeptides. Results The positive percentage of anti-I 1 and anti-I 2 were higher in SSc than in other groups（P 〈 0.05）. The sensitivity and specificity of anti-I 1 in SSc were 43.4% and 88.6%, and the sensitivity and specificity of anti-I 2 in SSc was 47.8% and 87.6%. There was no significant difference between the two peptides（P 〉 0.05）. Clinical characters and laboratory parameters were also compared to assess the clinical value of the antibodies in SSc. It showed that age, erythrocyte sedimentation rate, digestive tract involvement, pulmonary involvement had no significant difference between anti-I antibody positive and negative groups in SSe patients （P 〉 0.05）. But the positive groups had evidently shorter disease duration compared with negative groups （P 〈 0.05） . The antibodies and ANA, ACA, anti-Scl70 had no association with clinical presentations in SSc patients（P 〉 0.05）. Conclusions It has been showed by ELISA that the biologic technical software is helpful to design the epitopes of diffent protein at a certain extent. Polypeptides of I-1264-292 and I-441-461 has clinical value in SSc, particularly in the early stage of the disease. Their presence at the early stage of disease suggests that they may be helpful for early diagnosis.