抗核基质蛋白2抗体在特发性炎性肌病中的分布及临床意义

The prevalence and clinical usefulness of anti-NXP-2 autoantibodies in patients with idiopathic inflammatory myopathies

目的 检测特发性炎性肌病（IIM）患者血清中抗核基质蛋白2（NXP-2）抗体水平,探讨该抗体阳性的IIM患者的临床和实验室特征.方法 选取我院收治的IIM患者198例,其中幼年型皮肌炎（JDM）15例,DM 133例,PM 50例.其他CTD包括SLE 70例,RA 60例,SSc 15例,pSS 46例,MCTD 10例和健康对照60名.采用ELISA法测定上述人群血清中抗NXP-2抗体,抗体阳性血清采用免疫沉淀法进一步验证.采用t检验、Mann-Wittney U检验和x2检验等进行统计学分析.结果 血清抗NXP-2抗体在IIM中的阳性率为5.1％（10/198）,其中JDM组阳性率为20.0％（3/15）,DM组3.7％（5/133）,PM组4.0％（2/50）,3组间差异有统计学意义（P＜0.05）.而在其他CTD组及健康对照组的阳性率均为0.抗NXP-2抗体阳性的IIM患者发病年龄[（33±20）岁]低于抗体阴性组[（45±17）岁]（t=-2.09,P＜0.05）,皮下钙质沉积的发生率[30.0％（3/10）]高于抗体阴性组[2.6％（5/188）] （x2=0.7,P＜0.01）,而2组间性别、病程、关节炎、皮疹、近端肌无力、肌痛、吞咽困难、合并间质性肺病和肿瘤等的发生率差异无统计学意义.随访分析,10例抗体阳性的IIM患者中,3例为JDM,其中1例JDM在随访10个月后死亡,该患儿血清抗NXP-2抗体滴度明显升高,合并广泛的皮下钙质沉积,严重的肌无力和快速进展的病情.结论 本研究首次对我国IIM及其他CTD患者血清中抗NXP-2抗体进行检测,发现抗NXP-2抗体是IIM的特异性抗体,该抗体阳性者具有独特的临床表型.开展该抗体的检查对IIM诊断有重要价值,而且对IIM的临床分型有重要的指导意义.

Objective To determine the sera levels of anti-nuclear matrix protein （NXP）-2 autoantibodies and their clinical associations in patients with idiopathic inflammatory myopathies （IIM）.Methods Sera from 198 Chinese patients with IIM including 15 juvenile dermatomyositis （JDM）,133 dermatomyositis （DM） and 50 polymyositis （PM）,other connective tissue diseases （CTDs） including 70 systemic lupus erythematosus,60 rheumatoid arthritis,15 systemic sclerosis,46 primary Sj（o）gren syndrome,10 mixed connective tissue disease and 60 healthy controls were measured by enzyme linked immunosorbent assay.The anti-NXP-2 antibodies were detected.The positive sera were further examined by immunoprecipitation assays.Statistical analyses were performed using student＆#39;s t test or Mann-Wittney U test and x2 test.Results The positive rate of sera anti-NXP-2 autoantibodies in patients with IIM was 5.1% （10/198）,20.0% （3/15） in patients with JDM,3.7% （5/133） in patients with dermatomyositis,and 4.0%（2/50） in patients with polym-yositis.There was statistical significant difference in anti-NXP-2-positive rates between JDM,DM and PM （P〈0.05）.However,the autoantibody did not present in patients with other CTDs as well as healthy controls.The anti-NXP-2-positive patients had significantly younger age [（33±20） vs （45±17） years old （t=-2.09,P〈0.05）] and higher incidence of calcinosis [30.0%（3/10） vs 2.6%（15/188）] compared with the anti-NXP-2-negativepatients （x2=0.7,P〈0.01）.There were no statistical difference between the two groups in gender,disease duration,arthritis,rash,dysphagia,myasthenia,conccurrence with interstitial lung disease and cancer.In follow-up assessment,among the three JDM patients with anti-NXP-2 autoantibodies,one of them who died 10 months later had increased serum level of anti-NXP-2 autoantibody,extensive subcutaneous calcinosis,severe myasthenia and rapid progress.Conclusion This is the first report of the serum levels of anti-NXP-2 antibodies in Chinese patients with IIM and other CTDs.We find that anti-NXP-2 antibodies only exist in patients with IIM and are associated with early and calcinosis.