Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece.
Autoimmun Rev. 2013 Jul;12(9):924-30. doi: 10.1016/j.autrev.2013.03.002. Epub 2013 Mar 26.
Myasthenia gravis (MG) is the most common immune-mediated disorder of the neuromuscular junction with a prevalence of 200-300/million population and its study has established paradigms for exploring other antibody-mediated diseases. Most MG patients (~85%) have autoantibodies against the muscle acetylcholine receptor (AChR-MG), whereas about 6% of MG patients have autoantibodies against the muscle specific kinase (MuSK-MG). Until recently no autoantibodies could be detected in the remaining patients (seronegative MG). Probably, the most sensitive assays for the detection of the autoantibodies in MG sera have been the radioimmunoprecipitation assays (RIPA) for both types of MG. However, with recent novel methods, not yet used routinely, it has been shown that the "seronegative" MG group includes patients with low levels of autoantibodies or of low affinity, against the known autoantigens, or even with antibodies to recently identified autoantigens. Since MG is heterogeneous in terms of pathophysiology, depending on the autoantigen targeted and on other factors (e.g. presence of thymoma), the serological tests are crucial in verifying the initial clinical diagnosis, whereas frequent measurement of autoantibody levels is important in monitoring the course of the disease and the efficacy of treatment. In addition, in AChR-MG, autoantibodies against the muscle proteins titin and ryanodin receptor have been identified; these antibodies are useful for the classification of MG, indicating the concomitant presence of thymoma, and as prognostic markers.
重症肌无力(MG)是最常见的神经肌肉接头的免疫介导性疾病,患病率为 200-300/百万人,其研究为探索其他抗体介导性疾病建立了范例。大多数 MG 患者(~85%)具有针对肌肉乙酰胆碱受体(AChR-MG)的自身抗体,而约 6%的 MG 患者具有针对肌肉特异性激酶(MuSK-MG)的自身抗体。直到最近,在其余患者(血清阴性 MG)中仍无法检测到自身抗体。可能,用于检测 MG 血清中自身抗体的最敏感的检测方法一直是针对这两种类型 MG 的放射免疫沉淀检测(RIPA)。然而,最近使用尚未常规使用的新方法表明,“血清阴性”MG 组包括自身抗体水平低或亲和力低、针对已知自身抗原的患者,甚至包括针对最近鉴定的自身抗原的抗体。由于 MG 在病理生理学方面具有异质性,取决于针对的自身抗原以及其他因素(例如胸腺瘤的存在),血清学检测在验证初始临床诊断方面至关重要,而频繁测量自身抗体水平对于监测疾病过程和治疗效果也很重要。此外,在 AChR-MG 中,已鉴定出针对肌肉蛋白titin 和ryanodin 受体的自身抗体;这些抗体可用于 MG 的分类,表明同时存在胸腺瘤,并可作为预后标志物。