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Objective: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder of the peripheral nerves with an incompletely understood underlying pathophysiology. This investigation focused on defining B and T cell frequencies, T cell functional capacity and innate immune system analysis in patients with CIDP., Methods: By using multi-parameter flow cytometry, we examined the phenotype and function of PBMCs in 25 CIDP patients who were relatively clinically stable on treatment who met EFNS/PNS criteria, 21 patients with genetically confirmed hereditary neuropathy and 25 healthy controls. We also evaluated the regulatory T cell (Treg) inhibitory capacity by co-culturing Treg and effector T cells., Results: Proinflammatory CD4 T cells, especially type 1 helper T cell (Th1) and CD8 T cells in patients with CIDP were found to have an enhanced capacity to produce inflammatory cytokines. There was no difference in frequency of Th17 regulatory cells in CIDP patients versus healthy controls, however, Treg function was impaired in CIDP patients. There was no remarkable difference in innate immune system measures. Within B cell subsets, transitional cell frequency was decreased in CIDP patients., Interpretation: Patients with CIDP clinically stable on treatment continued to show evidence of a proinflammatory state with impaired Treg function. This potentially implies an inadequate suppression of ongoing inflammation not addressed by standard of care therapies as well as persistent activity of disease while on treatment. Targeting T cells, especially inhibiting Th1 and polyfunctional CD8 T cells or improving Treg cell function could be potential targets for future therapeutic research., Competing Interests: Declaration of competing interest YL: Research support from the MGFA and MGNet (U54 NS115054). JSY: None. JTG: Grant funding to support this research in this publication was provided by the GBS/CIDP foundation and the American Neuromuscular foundation. Stock or stock options are owned in Argenx. Currently an employee of Argenx, but previously during this grant work was an employee at Duke University. VCJ: None. LHW: Grant funding as a site investigator for clinical trials supported by Avidity Biosciences, Abcuro, Inc. and National Institutes of Health. Consultant honoraria paid by Alexion, Takeda and Helixmith. Honoraria for lectures at the AANEM annual meeting. SMR: Speaker at AANEM annual meeting and received personal honoraria for these presentations. Received Myasthenia Gravis Foundation of America support for attending meetings/travel. TK: Partial salary support in the past from the multi-site neurological disease biorepository grand funded by the myasthenia gravis foundation of American and the National Institutes of Health. KLG: Grant funding for support for the work presented in this paper was provided by the GBS/CIDP Foundation and the American Neuromuscular Foundation. Consultant, speaker and/or advisory board honoraria from Takeda, Immunovant, Argenx, Sanofi and Annexon. Service on the adjudication committee for clinical trials for Immunovant and Sanofi. Grant funding from the INC Base Registry Study. Honoraria payments for speaker presentations at AAN and AANEM., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To compare the immunopathology of immune checkpoint inhibitor-induced myasthenia gravis (ICI-MG) and idiopathic MG, we profiled the respective AChR autoantibody pathogenic properties. Of three ICI-MG patients with AChR autoantibodies, only one showed complement activation and modulation/blocking potency, resembling idiopathic MG. In contrast, AChR autoantibody-mediated effector functions were not detected in the other two patients, questioning the role of their AChR autoantibodies as key mediators of pathology. The contrasting properties of AChR autoantibodies in these cases challenge the accuracy of serological testing in establishing definite ICI-MG diagnoses and underscore the importance of a thorough clinical assessment when evaluating ICI-related adverse events., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Trial eligibility in myasthenia gravis (MG) remains largely dependent on a positive autoantibody serostatus. This significantly hinders seronegative MG (SNMG) patients from receiving potentially beneficial new treatments. In a subset of SNMG patients, acetylcholine receptor (AChR) autoantibodies are detectable by a clustered AChR cell-based assay (CBA). Of 99 SNMG patients from two academic U.S. centers, 18 (18.2%) tested positive by this assay. Autoantibody positivity was further validated in 17/18 patients. In a complementary experiment, circulating AChR-specific B cells were identified in a CBA-positive SNMG patient. These findings corroborate the clinical need for clustered AChR CBA testing when evaluating SNMG patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)