Novel pathophysiological insights in autoimmune myasthenia gravis.
Novel pathophysiological insights in autoimmune myasthenia gravis.
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DOI：
10.1097/wco.0000000000001088
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发表时间：
2022-10-01
影响因子：
4.8
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中科院分区：
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本文综述了近年来对自身免疫性重症肌无力（MG）免疫发病机制的研究进展。机制的理解是根据MG疾病亚型，并利用通过使用免疫调节生物疗法获得的知识。过去两年对MG的研究使MuSK自身抗体诱导病理的机制得到了更准确的定义。新的见解也出现在收集更有力的证据LRP 4自身抗体的致病能力。临床观察揭示了由癌症免疫治疗触发的新MG表型，但潜在的免疫生物学仍然不确定。从治疗的角度来看，MG患者现在可以从更广泛的治疗选择中受益。这些疗法已经揭示了AChR和MuSK MG亚型之间和内部的临床反应的深刻差异。两种亚型之间免疫病理学的不同机制，以及每个患者自身抗体库的定性细微差别，可能是治疗结果差异的基础。虽然缺乏临床反应的预测性生物标志物，但这些观察结果引发了可能有助于临床医生选择特定治疗策略的检测方法的发展。对自身抗体功能的最新进展使神经免疫学家更接近于更详细地了解MG病理学的机制。未来对MG患者免疫异质性的研究将是开发有效的、个体化治疗的关键。
This review summarizes recent insights into the immunopathogenesis of autoimmune myasthenia gravis (MG). Mechanistic understanding is presented according to MG disease subtypes and by leveraging the knowledge gained through the use of immunomodulating biological therapeutics. The past two years of research on MG have led to a more accurate definition of the mechanisms through which MuSK autoantibodies induce pathology. Novel insights have also emerged from the collection of stronger evidence on the pathogenic capacity of LRP4 autoantibodies. Clinical observations have revealed a new MG phenotype triggered by cancer immunotherapy, but the underlying immunobiology remains undetermined. From a therapeutic perspective, MG patients can now benefit from a wider spectrum of treatment options. Such therapies have uncovered profound differences in clinical responses between and within the AChR and MuSK MG subtypes. Diverse mechanisms of immunopathology between the two subtypes, as well as qualitative nuances in the autoantibody repertoire of each patient, likely underpin the variability in therapeutic outcomes. While predictive biomarkers of clinical response are lacking, these observations have ignited the development of assays that might assist clinicians in the choice of specific therapeutic strategies. Recent advances in the understanding of autoantibody functionalities are bringing neuroimmunologists closer to a more detailed appreciation of the mechanisms that govern MG pathology. Future investigations on the immunological heterogeneity among MG patients will be key to developing effective, individually tailored therapies.