抗Jo-1抗体在特发性炎性肌病临床分层及疾病谱中的意义

Significance of anti-Jo-1 antibody’s clinical stratification in idiopathic inflammatory myopathy and disease spectrum

目的:探究抗组氨酰tRNA合成酶(histidyl tRNA synthetase,Jo-1)抗体在特发性炎性肌病(idiopathic inflammatory myopathies,IIM)及其他疾病谱的意义。方法:入组北京大学人民医院2016—2022年利用免疫印迹法检测抗Jo-1抗体阳性的患者,同时入组抗Jo-1抗体阴性的抗合成酶综合征(anti-synthetase syndrome,ASS)患者作为对照,分析患者的基本信息、临床特征以及炎症和免疫学指标。结果:共入组165例抗Jo-1抗体阳性患者,结缔组织病(connective tissue disease,CTD)占80.6%(133/165),其中IIM占总数的57.6%(95/165),包括ASS(84/165,50.9%)、免疫介导坏死性肌病(7/165,4.2%)以及皮肌炎(4/165,2.4%),其他CTD占23.0%(38/165),包括类风湿关节炎(11/165,6.7%)、未分化结缔组织病(5/165,3.0%)、具有自身免疫特征的间质性肺炎(5/165,3.0%)、未分化关节炎(4/165,2.4%)、干燥综合征(3/165,1.8%)、系统性红斑狼疮(3/165,1.8%)和系统性血管炎(3/165,1.8%)等;其他疾病包括恶性肿瘤(3/165,1.8%)和感染(4/165,2.4%)等;未明确诊断患者占9.1%(15/165)。在ASS亚组分析中,抗Jo-1抗体阳性的ASS患者相比于抗体阴性者起病年龄更低(49.9岁vs.55.0岁,P=0.026),更多表现为关节炎(60.7%vs.33.3%,P=0.002)和肌痛(47.1%vs.22.2%,P=0.004)。ASS患者随着抗Jo-1抗体滴度的升高,关节炎、技工手、Gottron征、雷诺现象(Raynaud phenomenon)以及肌酸激酶、α-羟丁酸脱氢酶指标异常的发生率升高。抗Jo-1抗体阳性ASS患者在合并一种以上其他肌炎抗体阳性时,肌痛、肌无力的发生率升高(P<0.05)。结论:抗Jo-1抗体阳性患者疾病谱广,以ASS为主,但也可见于其他CTD、肿瘤、感染等疾病,应注意鉴别。

Objective:To investigate the significance of anti-histidyl tRNA synthetase(Jo-1)antibody in idiopathic inflammatory myopathies(IIM)and its diseases spectrum.Methods:We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People’s Hospital between 2016 and 2022.And the patients diagnosed with anti-synthetase antibody syndrome(ASS)with negative serum anti-Jo-1 antibody were enrolled as controls.We analyzed the basic information,clinical characteristics,and various inflammatory and immunological indicators of the patients at the onset of illness.Results:A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study.Among them,80.5%were diagnosed with connective tissue disease.And 57.6%(95/165)were diagnosed with IIM,including ASS(84/165,50.9%),immune-mediated necrotizing myopathy(7/165,4.2%)and dermatomyositis(4/165,2.4%).There were 23.0%(38/165)diagnosed with other connective tissue disease,mainly including rheumatoid arthritis(11/165,6.7%),undifferentiated connective tissue disease(5/165,3.0%),interstitial pneumonia with autoimmune features(5/165,3.0%),undifferentiated arthritis(4/165,2.4%),Sj gren’s syndrome(3/165,1.8%),systemic lupus erythematosus(3/165,1.8%),systemic vasculitis(3/165,1.8%),and so on.Other cases included 3(1.8%)malignant tumor patients,4(2.4%)infectious cases and so on.The diagnoses were not clear in 9.1%(15/165)of the cohort.In the analysis of ASS subgroups,the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody(49.9 years vs.55.0 years,P=0.026).Clinical manifestations of arthritis(60.7%vs.33.3%,P=0.002)and myalgia(47.1%vs.22.2%,P=0.004)were more common in the ASS patients with positive anti-Jo-1 antibody.With the increase of anti-Jo-1 antibody titer,the incidence of the manifestations of arthritis,mechanic hands,Gottron sign and Raynaud phenomenon increased,and the proportion of abnormal creatine kinase andα-hydroxybutyric dehydrogenase index increased in the ASS patients.The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies(P<0.05).Conclusion:The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases,mainly ASS.And anti-Jo-1 antibody can also be found in many connective tissue diseases,malignant tumor,infection and so on.