Myasthenie.com

Brain Sci. 2025 Sep 11;15(9):978. doi: 10.3390/brainsci15090978.

ABSTRACT

BACKGROUND: Generalized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies.

OBJECTIVE: This review aims to synthesize current knowledge of the immunopathological mechanisms across gMG subtypes and to explore emerging therapeutic targets tailored to these diverse disease phenotypes.

METHODS: A narrative review was conducted, integrating recent findings from clinical trials, immunogenetic studies, and preclinical research to describe subtype-specific immune mechanisms and corresponding therapeutic innovations.

RESULTS: gMG subtypes-characterized by autoantibody profiles (AChR, MuSK, LRP4, or seronegative), thymic histopathology, and age of onset-demonstrate distinct immunological pathways. Early-onset MG is associated with thymic hyperplasia and Th17-driven inflammation; thymoma-associated MG involves central tolerance breakdown; late-onset MG shows immune senescence and altered T-cell regulation. MuSK- and LRP4-positive MG exhibit unique cytokine and antibody signatures. Novel therapeutic strategies include B cell- and T cell-targeted therapies (e.g., anti-CD19, anti-CD38, JAK inhibitors), cytokine inhibitors (IL-6, IL-17, IL-23), FcRn antagonists, complement inhibitors, and gene- or cell-based therapies such as CAR-T and CAAR-T cells.

CONCLUSION: The evolving landscape of gMG treatment reflects a shift toward immunopathology-based precision medicine. Better characterization of subtype-specific molecular signatures and immune dysfunctions is essential to guide clinical decision-making and improve outcomes for treatment-refractory patients.

PMID:41008338 | DOI:10.3390/brainsci15090978


Source: https://pubmed.ncbi.nlm.nih.gov/4100833 ... t9+e462414