{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:57:46Z","timestamp":1790229466578,"version":"4.1.0"},"reference-count":199,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>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\u2014characterized by autoantibody profiles (AChR, MuSK, LRP4, or seronegative), thymic histopathology, and age of onset\u2014demonstrate 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.<\/jats:p>","DOI":"10.3390\/brainsci15090978","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T10:50:04Z","timestamp":1757587804000},"page":"978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunological Targets in Generalized Myasthenia Gravis Treatment: Where Are We Going Now?"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7862-6743","authenticated-orcid":false,"given":"Elena","family":"Rossini","sequence":"first","affiliation":[{"name":"NESMOS Department, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Leonardi","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Center, Sant\u2019Andrea Hospital, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Morino","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Center, Sant\u2019Andrea Hospital, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Antonini","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Center, Sant\u2019Andrea Hospital, 00185 Rome, Italy"},{"name":"UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8813-2272","authenticated-orcid":false,"given":"Laura","family":"Fionda","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Center, Sant\u2019Andrea Hospital, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"McCallion, J., Borsi, A., Noel, W., Lee, J., Karmous, W., Sattler, S., Boggia, G., Hardy, E., Mitchell, C., and Mitchell, S. 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