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提高重症肌无力的实验室诊断水平。

Improving laboratory diagnostics in myasthenia gravis.

机构信息

Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy.

Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.

出版信息

Expert Rev Mol Diagn. 2021 Jun;21(6):579-590. doi: 10.1080/14737159.2021.1927715. Epub 2021 May 19.

Abstract

: Myasthenia gravis (MG) is a prototypical autoimmune disease, characterized by pathogenic autoantibodies targeting structures of the neuromuscular junction. Radioimmunoprecipitation assays (RIPAs) represent the gold standard for their detection. However, new methods are emerging to complement, or overcome RIPAs, also with the perspective of eliminating the use of radioactive reagents.: We discuss advances in laboratory methods, prompted especially by cell-based assays (CBAs), for the detection of the autoantibodies of MG diagnostics, above all those to the nicotinic acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and low molecular-weight receptor-related low-density lipoprotein-4 (LRP4).: CBA technology makes AChRs aggregate on cell membranes, thus allowing to detect autoantibodies to clustered AChRs, with reduction of seronegative MG cases. The diagnostic relevance of RIPA/CBA-measurable LRP4 antibodies is still unclear, in Caucasian patients at least. Live CBAs for the detection of AChR, MuSK, and LRP4 antibodies might represent an alternative to RIPAs, but first require full validation. CBAs could be used as screening tests, limiting RIPAs for antibody quantification. To this end, ELISAs might be an alternative.Fixation procedures preserving enough degree of antigen conformationality could yield AChR and MuSK CBAs suitable for a wide use in clinical-chemistry laboratories.

摘要

重症肌无力(MG)是一种典型的自身免疫性疾病,其特征是致病性自身抗体针对神经肌肉接头的结构。放射免疫沉淀测定(RIPA)是其检测的金标准。然而,新的方法正在涌现,以补充或克服 RIPA,也有消除放射性试剂使用的观点。

我们讨论了实验室方法的进展,特别是由于基于细胞的测定(CBAs),用于检测 MG 诊断的自身抗体,尤其是那些针对烟碱型乙酰胆碱受体(AChR)、肌肉特异性激酶(MuSK)和低分子量受体相关低密度脂蛋白-4(LRP4)的自身抗体。

CBA 技术使 AChR 在细胞膜上聚集,从而可以检测到聚集的 AChR 自身抗体,减少了血清阴性 MG 病例。至少在白种人群中,RIPA/CBA 可测量的 LRP4 抗体的诊断相关性仍不清楚。用于检测 AChR、MuSK 和 LRP4 抗体的活 CBA 可能是 RIPA 的替代方法,但首先需要充分验证。CBA 可作为筛选试验,限制 RIPA 用于抗体定量。为此,ELISA 可能是一种替代方法。

保持足够抗原构象程度的固定程序可以产生适合于临床化学实验室广泛使用的 AChR 和 MuSK CBA。

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