PERIPHERAL NERVE AND NEURO-MUSCULAR JUNCTION DISEASE: Edited by Luis QuerolNovel pathophysiological insights in autoimmune myasthenia gravisMasi, Gianvitoa,b; O’Connor, Kevin C.a,b Author Information aDepartment of Neurology bDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA Correspondence to Kevin C. O’Connor, PhD, Yale School of Medicine, 300 George Street Room 353J, New Haven, CT 06511, USA. Tel: +1 203 737 3321; e-mail: [email protected] Current Opinion in Neurology 35(5):p 586-596, October 2022. | DOI: 10.1097/WCO.0000000000001088 Buy Metrics Abstract Purpose of review This review summarizes recent insights into the immunopathogenesis of autoimmune myasthenia gravis (MG). Mechanistic understanding is presented according to MG disease subtypes and by leveraging the knowledge gained through the use of immunomodulating biological therapeutics. Recent findings The past two years of research on MG have led to a more accurate definition of the mechanisms through which muscle-specific tyrosine kinase (MuSK) autoantibodies induce pathology. Novel insights have also emerged from the collection of stronger evidence on the pathogenic capacity of low-density lipoprotein receptor-related protein 4 autoantibodies. Clinical observations have revealed a new MG phenotype triggered by cancer immunotherapy, but the underlying immunobiology remains undetermined. From a therapeutic perspective, MG patients can now benefit from a wider spectrum of treatment options. Such therapies have uncovered profound differences in clinical responses between and within the acetylcholine receptor and MuSK MG subtypes. Diverse mechanisms of immunopathology between the two subtypes, as well as qualitative nuances in the autoantibody repertoire of each patient, likely underpin the variability in therapeutic outcomes. Although predictive biomarkers of clinical response are lacking, these observations have ignited the development of assays that might assist clinicians in the choice of specific therapeutic strategies. Summary Recent advances in the understanding of autoantibody functionalities are bringing neuroimmunologists closer to a more detailed appreciation of the mechanisms that govern MG pathology. Future investigations on the immunological heterogeneity among MG patients will be key to developing effective, individually tailored therapies. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.