The immune microenvironment and population heterogeneity in myasthenia gravis: implications for precision therapeutics
Myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction characterized by fluctuating skeletal muscle weakness. Although the pathogenic roles of autoantibodies targeting the acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and certain neuromuscular junction proteins have been well established, increasing evidence indicates that MG onset, progression, and therapeutic response can be shaped by the complex interactions within diverse immune microenvironments. Particularly, population heterogeneity, including differences in antibody subtype, age, sex, genetic susceptibility, ethnicity, thymic pathology, and potential confounders related to differences in healthcare conditions, strongly contributes to variability in its clinical manifestations and targeted therapies. This review discusses current evidence on the roles of the immune microenvironment and individual heterogeneity in shaping the pathogenesis and treatment landscape of MG. Along with the contributions of immunophenotyping, multi-omics techniques, single-cell and spatial transcriptomics, and biomarker discovery in improving our understanding of MG mechanisms, we also evaluated the implications of immune diversity in various populations for established therapies, as well as emerging immune-modulating approaches. This review highlights current knowledge gaps and future research priorities, emphasizing the transition from phenotype-based disease classification toward immune endotype-driven precision medicine within population heterogeneity.