{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:10:41Z","timestamp":1790086241298,"version":"4.0.1"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Myasthenia gravis (MG) is a heterogeneous neuroimmune disorder in which pathogenic autoantibodies impair neuromuscular junction transmission and produce fluctuating skeletal muscle weakness. Although conventional therapy with acetylcholinesterase inhibitors, corticosteroids, and broad immunosuppressants remains effective for many patients, its limitations are increasingly evident, including delayed onset, cumulative toxicity, and inadequate control in refractory disease. These challenges have accelerated the transition from non-selective immunosuppression to biologic and other targeted therapies. Recent advances in MG have revealed that treatment response is strongly shaped by disease heterogeneity across molecular, cellular, and structural levels. Antibody-defined subtypes, including acetylcholine receptor (AChR)-positive, muscle-specific tyrosine kinase (MuSK)-positive, low-density lipoprotein receptor-related protein 4 (LRP4)-positive, and seronegative MG, differ in immune mechanism, complement dependence, and therapeutic vulnerability. On this basis, neonatal Fc receptor (FcRn) antagonists, complement inhibitors, and B-cell-directed therapies have emerged as major biologic classes that increasingly enable mechanism-informed treatment selection. At the same time, resistance remains an important clinical problem, arising from persistent autoreactive immune compartments, pathway-level escape, and irreversible neuromuscular junction damage that may sustain disability despite immunological control. In this review, we discuss how immunological heterogeneity provides the biological rationale for targeted therapy in MG and synthesize current evidence for established and emerging biologics, including FcRn antagonists, complement inhibitors, B-cell- and plasma-cell-directed strategies, and cell-based immunotherapies. We further examine the major barriers that now define the field, particularly long-term safety, infection risk, treatment resistance, incomplete biomarker frameworks, and the distinction between active immune refractoriness and fixed structural impairment. Finally, we outline how biomarker-guided stratification, dynamic monitoring, and integration of neuroprotective or regenerative approaches may help move MG management from empiric escalation toward safer and more precise individualized care.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1929054","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:58:13Z","timestamp":1790085493000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Myasthenia gravis: from recognition of heterogeneity to a paradigm shift toward precision therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhao-qing","family":"Li","sequence":"first","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]},{"name":"The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-yue","family":"Deng","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-jun","family":"Qiao","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-feng","family":"Xie","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-peng","family":"Huang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine","place":["Shenyang, 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