免疫介导坏死性肌病的临床和病理特征分析

目的 比较不同肌炎特异性自身抗体(myositis specific antibodies,MSAs)类型的免疫介导坏死性肌病(immune-mediated necrotizing myopathies,IMNM)的临床和病理特征。方法 从中日友好医院2008—2018年住院期间所有行肌肉活检的特发性炎性肌病患者中选取符合以下任一条件的IMNM患者104例:(1)抗信号识别颗粒(signal recognition particle,SRP)抗体阳性;(2)抗3-羟基-3-甲基戊二酰辅酶A 还原酶(3-hydroxy-3-methylglutaryl-coenzyme A reductase,HMGCR)抗体阳性;(3)血清MSAs阴性且病理符合2004年欧洲神经肌肉病中心定义的IMNM病理诊断标准。回顾性收集患者的临床、实验室检查和肌肉病理等信息,比较各组临床及病理特征的差异。结果 所有104例IMNM患者中,肌无力(92.3%)、肌酸激酶升高(92.3%)是IMNM的最常见临床表现,此外,33.7%的IMNM患者合并吞咽困难,46.5%的患者合并间质性肺病(interstitial lung diseases,ILD)。抗HMGCR阳性患者较抗SRP阳性和MSAs阴性患者更容易出现V形疹(30.4% vs. 4.3%和5.9%,P<0.01),抗SRP阳性患者合并ILD发生率高于抗HMGCR阳性和MSAs阴性患者(64.4% vs. 34.8%和29.0%,P<0.01),MSAs阴性患者合并其他结缔组织病更多见(32.4% vs. 8.5%和4.3%,P<0.01)。3组IMNM患者肌肉病理中均可见肌细胞坏死(94.2%)、吞噬(65.4%)和再生(67.3%),肌细胞膜表达主要组织相容性复合物-Ⅰ分子上调(78.8%),肌内膜CD4 ⁺T细胞(68.3%)和CD68 ⁺巨噬细胞(65.7%)浸润。结论 抗SRP抗体阳性、抗HMGCR抗体阳性和MSAs阴性的IMNM患者存在异质性,在临床上开展MSAs检测和肌肉病理检查对区分不同类型的IMNM有指导价值。

Clinical and pathological characteristics of immune mediated necrotizing myopathy

Objective: To investigate the clinical and pathological features of immune-mediated necro-tic myopathies (IMNM) with different myositis-specific antibodies (MSAs).Methods: In the study, 104 IMNM patients who met any of the following three criteria were selected from idiopathic inflammatory myopathy patients who had MSAs results and underwent muscle biopsy from 2008 to 2018 in China-Japan Friendship Hospital: (1) Anti-signal recognition particle (SRP) antibody positive; (2) Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) antibody positive; (3) MSAs negative and consistent with the pathological diagnostic criteria of IMNM defined by the European Neuromuscular Centre in 2004. The clinical, laboratory and muscle pathological information of the IMNM patients were retrospectively collected and compared in anti-SRP, anti-HMGCR and MSAs negative groups.Results: Of 104 IMNM patients, 47 patients (45.2%) were positive for anti-SRP antibody, 23 (22.1%) were positive for anti-HMGCR antibody, and 34 (32.7%) were negative for MSAs. The common symptoms of IMNM patients were muscle weakness (92.3%), elevated serum creatine kinase level (92.3%), dysphagia (33.7%) and interstitial lung diseases (ILD) (49.5%). The anti-HMGCR-positive patients were more frequent to have “V” sign (30.4% vs. 4.3% and 5.9%, P<0.01) as compared with the anti-SRP-positive and MSAs-negative patients. The incidence of ILD in the anti-SRP-positive patients was higher than that in the anti-HMGCR-positive and MSAs negative patients (64.4% vs. 34.8% and 29.0%, P<0.01). The prevalence of the patients combined with other connective tissue diseases in MSAs-negative IMNM was higher than that in the other two groups (32.4% vs. 8.5% and 4.3%, P<0.01). 93.3% of the anti-SRP-positive patients were found with antinuclear antibody positivity, higher than those of the anti-HMGCR-positive and MSAs-negative patients (93.3% vs. 36.4% and 58.8%, P<0.001). The common pathological features of IMNM were muscle fibre necrosis (94.2%), regeneration (67.3%) and phagocytosis (65.4%), overexpression of major histocompatibility complex-1 on sarcolemma (78.8%), infiltration of CD4 ⁺ T cells (81.7%) and CD68 ⁺ macrophage (79.8%) and expression of membrane attack complex (MAC) (77.8%). The endomysial infiltration of CD4 ⁺ T cells and CD68 ⁺ macrophage and MAC expression on sarcolemma in the MSAs-negative group were more common than that in the anti-SRP and anti-HMGCR groups (88.2% vs. 57.4% and 60.9%, 91.2% vs. 59.1% and 38.1%, 76.5% vs. 45.5% and 42.9%, respectively, P<0.01).Conclusion: There is heterogeneity in anti-SRP-positive, anti-HMGCR-positive or MSAs-negative patients. The detection of MSAs and performing of muscle biopsy are useful for distinguishing different types of IMNM.