Correlation of Anti-Signal Recognition Particle Autoantibody Levels With Creatine Kinase Activity in Patients With Necrotizing Myopathy

Correlation of Anti-Signal Recognition Particle Autoantibody Levels With Creatine Kinase Activity in Patients With Necrotizing Myopathy
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DOI:
10.1002/art.30344
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发表时间:
2011-07-01
影响因子:
--
通讯作者:
Boyer, Olivier
Boyer, Olivier
中科院分区:
其他
文献类型:
--
作者:
Benveniste, Olivier;Drouot, Laurent;Boyer, Olivier

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目标。抗信号识别颗粒(抗srp)自身抗体与严重的获得性坏死性肌病有关。这些自身抗体的作用仍然难以捉摸,抗srp水平随时间的演变是未知的。在这项研究中,我们开发了一种定位激光头免疫测定(ALBIA)技术来研究坏死性肌病患者的抗srp水平、血清肌酸激酶(CK)水平和肌肉力量之间的关系。通过比较31名抗srp免疫点阳性患者与190名健康献血者和199名患有不同炎症/自身免疫性疾病或多克隆高γ球蛋白血症的对照患者的血清抗srp自身抗体水平,确定ALBIA检测的诊断价值。在31例抗srp阳性患者中,8例患者的血清样本被长期监测抗srp自身抗体水平和CK水平(在平均783天的随访期间连续检测至少3次)。采用线性混合模型检测抗srp自身抗体水平与CK水平之间的关系。在所有抗srp免疫点阳性血清样本中,该检测结果均为抗srp阳性,而所有对照血清均为阴性。8例抗srp阳性患者经纵向随访发现CK水平正常,肌力改善。在接受治疗的患者中,CK水平测量的肌溶解程度与这些患者的抗srp54自身抗体水平之间存在显著的相关性(P = 0.002)。抗srp阳性肌炎似乎是少数几种自身免疫性疾病之一,其中特异性自身抗体水平与替代疾病活动标志物相关。这些结果揭示了在接受治疗的患者中监测抗srp自身抗体水平的有效性,也可能提示抗srp自身抗体在坏死性肌病中的可能致病作用。
Objective. Anti-signal recognition particle (anti-SRP) autoantibodies are associated with severe acquired necrotizing myopathies. The role of these autoantibodies remains elusive, and the evolution of anti-SRP levels over time is unknown. In this study, we developed an addressable laser bead immunoassay (ALBIA) technique to investigate a correlation between anti-SRP levels, serum creatine kinase (CK) levels, and muscle strength in patients with necrotizing myopathy.Methods. The diagnostic value of the ALBIA assay was determined by comparing serum levels of anti-SRP autoantibodies in 31 anti-SRP immunodot-positive patients to those in 190 healthy blood donors and 199 control patients with different inflammatory/autoimmune conditions or polyclonal hypergammaglobulinemia. Among the 31 anti-SRP-positive patients, serum samples from 8 patients were monitored over time for levels of anti-SRP autoantibodies and levels of CK (determined at least 3 times, consecutively, over a mean followup period of 783 days). The relationship between levels of anti-SRP autoantibodies and levels of CK was tested using a linear mixed model.Results. The assay yielded positive results for anti-SRP in all anti-SRP immunodot-positive serum samples tested, while all control sera tested negative. The 8 anti-SRP positive patients who were followed up longitudinally were found to have normalized CK levels and improved muscle strength. There was a striking correlation between the degree of myolysis, as measured by CK levels, in patients receiving therapy and the anti-SRP54 autoantibody levels in these same patients (P = 0.002).Conclusion. Anti-SRP-positive myositis appears to be one of the few autoimmune diseases in which specific autoantibody levels are correlated with surrogate disease activity markers. These results reveal the usefulness of monitoring anti-SRP autoantibody levels in patients receiving therapy, and may also suggest a possible pathogenic role for anti-SRP autoantibodies in the necrotizing myopathies.