[Pubmed] Exosomes for myasthenia gravis: unraveling pathogenic insights and pioneering therapies

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Clin Chim Acta. 2026 Apr 20:121020. doi: 10.1016/j.cca.2026.121020. Online ahead of print.

ABSTRACT

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by pathogenic autoantibodies targeting the neuromuscular junction, leading to fatigable muscle weakness. While traditional and novel biologic therapies have advanced management, the complex immunopathology necessitates deeper mechanistic insights and improved diagnostic tools. Exosomes-small extracellular vesicles secreted by virtually all cell types-have emerged as pivotal players in intercellular communication, immune regulation, and disease propagation. This review synthesizes current evidence on the multifaceted roles of exosomes in MG. We detail their therapeutic potential, highlighting how engineered exosomes from tolerogenic dendritic cells or mesenchymal stem cells can deliver immunomodulatory cargo (e.g., miR-146a, caspase-1 inhibitors) to restore immune tolerance, suppress pathogenic antibody production, and ameliorate disease in experimental models. We explore their diagnostic utility as reservoirs of stable biomarkers, where dysregulated exosomal microRNAs (e.g., miR-106a-5p, miR-150-5p) and long non-coding RNAs correlate with disease severity, subtype, and treatment response, offering promise for non-invasive monitoring, especially in seronegative MG. Furthermore, we examine pathogenic mechanisms, whereby exosomal cargos may disrupt central thymic tolerance, amplify B- and T-cell activation via lncRNA-mediated miRNA sequestration, and contribute to neuromuscular dysfunction. By integrating findings across these domains, this review positions exosomes as critical mediators linking immune dysregulation to clinical manifestations in MG. Their dual nature as both disease contributors and therapeutic vehicles underscores their translational significance, paving the way for novel biomarker-driven strategies and targeted, cell-free immunotherapies in the precision medicine era.

PMID:42019752 | DOI:10.1016/j.cca.2026.121020


Source: https://pubmed.ncbi.nlm.nih.gov/4201975 ... t6+133c1fe