Werner Jessie L, Christopher-Stine Lisa, Ghazarian Sharon R, Pak Katherine S, Kus Jordan E, Daya Natalie R, Lloyd Thomas E, Mammen Andrew L
Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Arthritis Rheum. 2012 Dec;64(12):4087-93. doi: 10.1002/art.34673.
Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are found in patients with statin-associated immune-mediated necrotizing myopathy and, less commonly, in statin-unexposed patients with autoimmune myopathy. The main objective of this study was to define the association of anti-HMGCR antibody levels with disease activity.
Anti-HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti-HMGCR-positive patients. Associations of antibody level with CK level and strength at visit 1 were analyzed in 55 patients, 40 of whom were exposed to statins. In 12 statin-exposed and 5 statin-unexposed patients with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated.
Antibody levels were associated with CK levels (P < 0.001), arm strength (P < 0.05), and leg strength (P < 0.05) at visit 1, but these associations were only significant among statin-exposed patients in stratified analyses. With immunosuppressive treatment over 26.2 ± 12.6 months (mean ± SD), antibody levels declined (P < 0.05) and arm abduction strength improved (P < 0.05) in the 17 patients followed up longitudinally. The separate analysis showed that statin-exposed patients developed decreased antibody levels (P < 0.01), decreased CK levels (P < 0.001), improved arm strength (P < 0.05), and improved hip flexion strength (P < 0.05) with treatment. Anti-HMGCR antibody levels did not normalize in any patient.
In the entire cohort, initial anti-HMGCR levels correlated with indicators of disease activity; with immunosuppressive treatment, antibody levels declined and arm strength improved. Statin-exposed patients had significant improvements in CK levels and strength whereas statin-unexposed patients did not, suggesting a phenotypic difference between statin-exposed and statin-unexposed anti-HMGCR-positive patients.
在他汀类药物相关免疫介导坏死性肌病患者中可检测到识别3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）的自身抗体，在未使用他汀类药物的自身免疫性肌病患者中也较少见。本研究的主要目的是确定抗HMGCR抗体水平与疾病活动度之间的关联。
对抗HMGCR阳性患者评估抗HMGCR水平、肌酸激酶（CK）水平和肌力。分析了55例患者在首次就诊时抗体水平与CK水平及肌力的关联，其中40例患者曾使用他汀类药物。对12例使用他汀类药物和5例未使用他汀类药物的患者进行了5次连续随访，研究抗体水平、CK水平和肌力的变化情况。
在首次就诊时，抗体水平与CK水平（P<0.001）、上肢肌力（P<0.05）和下肢肌力（P<0.05）相关，但在分层分析中，这些关联仅在使用他汀类药物的患者中具有统计学意义。在17例接受纵向随访的患者中，经过26.2±12.6个月（均值±标准差）的免疫抑制治疗后，抗体水平下降（P<0.05），上肢外展肌力改善（P<0.05）。单独分析显示，使用他汀类药物的患者经治疗后抗体水平下降（P<0.01）、CK水平下降（P<0.001）、上肢肌力改善（P<0.05）、髋关节屈曲肌力改善（P<0.05）。所有患者的抗HMGCR抗体水平均未恢复正常。
在整个队列中，初始抗HMGCR水平与疾病活动指标相关；经过免疫抑制治疗后，抗体水平下降，上肢肌力改善。使用他汀类药物的患者CK水平和肌力有显著改善，而未使用他汀类药物的患者则无改善，提示使用他汀类药物和未使用他汀类药物的抗HMGCR阳性患者存在表型差异。
