{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T14:55:38Z","timestamp":1794408938586,"version":"4.9.0"},"reference-count":48,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Jackie McSpadden Postdoctoral Fellowship from the Myasthenia Gravis Foundation of America","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health","award":["R01-AI114780, R21-AI164590"],"award-info":[{"award-number":["R01-AI114780, R21-AI164590"]}]},{"name":"NIH T32 predoctoral training grant","award":["T32AI007019-46"],"award-info":[{"award-number":["T32AI007019-46"]}]},{"DOI":"10.13039\/100018748","name":"Argenx","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100018748","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2026,5,13]]},"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Efgartigimod, a neonatal Fc receptor (FcRn) blocker, effectively reduces total IgG, including pathogenic acetylcholine receptor (AChR) autoantibodies in myasthenia gravis (MG); however, clinical responses vary. To investigate this variability, we studied how efgartigimod impacts AChR-specific autoantibody profiles and associated pathogenic mechanisms, including complement activation, AChR internalisation and ACh-binding site blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum samples (N=150) were sourced from 50 AChR autoantibody-positive generalised MG patients participating in the phase 3 ADAPT study, randomised to receive efgartigimod (N=40) or placebo (N=10) in cycles of 4-weekly infusions. Samples were collected at baseline, day 29 and day 57 during the first cycle. Live cell-based assays quantified AChR-specific IgG subclasses and isotypes and assessed their capacity to mediate pathomechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Efgartigimod decreased all detectable AChR-specific IgG subclasses. At baseline, AChR autoantibody-mediated C3b deposition, AChR internalisation and ACh-binding site blockade were detected in 42 (84%), 41 (82%) and 10 (20%) patients, respectively. After 4-weekly infusions of efgartigimod, the magnitude of all three pathomechanisms was significantly decreased. However, the extent of this reduction varied across individuals. Double responders on both MG-activities of daily living and quantitative MG scores demonstrated a greater reduction in complement activity and AChR internalisation compared with patients who responded on only one score or were double non-responders. In addition, efgartigimod reduced IgG-dependent IgM binding to AChR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that clinical efficacy may be more closely associated with functional modulation of the AChR-specific autoantibodies than with their absolute quantity alone. These results support the evaluation of mechanistic pathway monitoring as a potential strategy to predict or guide efgartigimod treatment response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2025-338323","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T17:20:33Z","timestamp":1780593633000},"page":"923-935","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Pathogenic properties of myasthenia gravis AChR autoantibodies associate with clinical response to efgartigimod"],"prefix":"10.1136","volume":"97","clinical-trial-number":[{"clinical-trial-number":"nct03669588","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3790-4946","authenticated-orcid":false,"given":"Fatemeh","family":"Khani-Habibabadi","sequence":"first","affiliation":[{"name":"Neurology, Yale School of Medicine, New Haven, Connecticut, USA"},{"name":"Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2470-6910","authenticated-orcid":false,"given":"Fien M","family":"Verhamme","sequence":"additional","affiliation":[{"name":"argenx BV, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0287-1049","authenticated-orcid":false,"given":"Mahan","family":"Moshir","sequence":"additional","affiliation":[{"name":"argenx BV, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8574-1231","authenticated-orcid":false,"given":"Tine","family":"Casneuf","sequence":"additional","affiliation":[{"name":"argenx BV, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9290-7050","authenticated-orcid":false,"given":"Vijayaraghava T S","family":"Rao","sequence":"additional","affiliation":[{"name":"argenx BV, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8989-130X","authenticated-orcid":false,"given":"Sophie","family":"Steeland","sequence":"additional","affiliation":[{"name":"argenx BV, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2560-2732","authenticated-orcid":false,"given":"Peter","family":"Ulrichts","sequence":"additional","affiliation":[{"name":"argenx BV, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0234-4790","authenticated-orcid":false,"given":"Minh C","family":"Pham","sequence":"additional","affiliation":[{"name":"Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Nowak","sequence":"additional","affiliation":[{"name":"Neurology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-6310","authenticated-orcid":false,"given":"Bhaskar","family":"Roy","sequence":"additional","affiliation":[{"name":"Neurology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7056-419X","authenticated-orcid":false,"given":"Kevin C","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Neurology, Yale School of Medicine, New Haven, Connecticut, USA"},{"name":"Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"2026091402101043000_97.10.923.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02493-6"},{"key":"2026091402101043000_97.10.923.2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-023-02603-y"},{"key":"2026091402101043000_97.10.923.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.03.004"},{"key":"2026091402101043000_97.10.923.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2010.03019.x"},{"key":"2026091402101043000_97.10.923.5","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30369-1"},{"key":"2026091402101043000_97.10.923.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-023-11699-x"},{"key":"2026091402101043000_97.10.923.7","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-010-9468-4"},{"key":"2026091402101043000_97.10.923.8","doi-asserted-by":"publisher","DOI":"10.1172\/jci97911"},{"key":"2026091402101043000_97.10.923.9","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(21)00159-9"},{"key":"2026091402101043000_97.10.923.10","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000200436","article-title":"AChR Autoantibody Pathogenic Properties Are Heterogeneously Distributed and Undergo Temporal Changes Among Patients With Myasthenia Gravis","volume":"12","author":"Khani-Habibabadi","year":"2025","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2026091402101043000_97.10.923.11","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms1608","article-title":"Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential","volume":"2","author":"Stapleton","year":"2011","journal-title":"Nat Commun"},{"key":"2026091402101043000_97.10.923.12","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1093\/brain\/awn092","article-title":"IgG1 antibodies to acetylcholine receptors in \u201cseronegative\u201d myasthenia gravis","volume":"131","author":"Leite","year":"2008","journal-title":"Brain (Bacau)"},{"key":"2026091402101043000_97.10.923.13","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801295"},{"key":"2026091402101043000_97.10.923.14","doi-asserted-by":"crossref","first-page":"577850","DOI":"10.1016\/j.jneuroim.2022.577850","article-title":"The clinical need for clustered AChR cell-based assay testing of seronegative MG","volume":"367","author":"Masi","year":"2022","journal-title":"J Neuroimmunol"},{"key":"2026091402101043000_97.10.923.15","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21802"},{"key":"2026091402101043000_97.10.923.16","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000001169","article-title":"Heterogeneity of Acetylcholine Receptor Autoantibody-Mediated Complement Activity in Patients With Myasthenia Gravis","volume":"9","author":"Obaid","year":"2022","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2026091402101043000_97.10.923.17","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.165373","article-title":"MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity","volume":"8","author":"Yandamuri","year":"2023","journal-title":"JCI Insight"},{"key":"2026091402101043000_97.10.923.18","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqv009"},{"key":"2026091402101043000_97.10.923.19","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(96)12488-5"},{"key":"2026091402101043000_97.10.923.20","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPYEOR6SGE8ZLU"},{"key":"2026091402101043000_97.10.923.21","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/285238a0","article-title":"Myasthenia gravis induced by monoclonal antibodies to acetylcholine receptors","volume":"285","author":"Lennon","year":"1980","journal-title":"Nature New Biol"},{"key":"2026091402101043000_97.10.923.22","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/acn3.311","article-title":"Compromised fidelity of B-cell tolerance checkpoints in AChR and MuSK myasthenia gravis","volume":"3","author":"Lee","year":"2016","journal-title":"Ann Clin Transl Neurol"},{"key":"2026091402101043000_97.10.923.23","doi-asserted-by":"crossref","unstructured":"Bayer AC , Sanmarco LM , Pellerin A , et al . Therapeutic IgG- and IgM-specific proteases disarm the acetylcholine receptor autoantibodies that drive myasthenia gravis pathology. Proc Natl Acad Sci USA 2025;122. doi:10.1073\/pnas.2505984122","DOI":"10.1073\/pnas.2505984122"},{"key":"2026091402101043000_97.10.923.24","first-page":"82","article-title":"Acetylcholine receptor antibody in myasthenia gravis: predominance of IgG subclasses 1 and 3","volume":"67","author":"R\u00f8dgaard","year":"1987","journal-title":"Clin Exp Immunol"},{"key":"2026091402101043000_97.10.923.25","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(81)90015-1"},{"key":"2026091402101043000_97.10.923.26","first-page":"257","article-title":"Acetylcholine receptor antibody characteristics in myasthenia gravis. I. Patients with generalized myasthenia or disease restricted to ocular muscles","volume":"49","author":"Vincent","year":"1982","journal-title":"Clin Exp Immunol"},{"key":"2026091402101043000_97.10.923.27","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1212\/WNL.39.10.1359","article-title":"Diagnostic significance of IgG, C3, and C9 at the limb muscle motor end\u2010plate in minimal myasthenia gravis","volume":"39","author":"Tsujihata","year":"1989","journal-title":"Neurology (ECronicon)"},{"key":"2026091402101043000_97.10.923.28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1987.tb51301.x"},{"key":"2026091402101043000_97.10.923.29","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/00005072-198003000-00005","article-title":"Ultrastructural Localization of the Terminal and Lytic Ninth Complement Component (C9) at the Motor End-plate in Myasthenia Gravis","volume":"39","author":"Sahashi","year":"1980","journal-title":"J Neuropathol Exp Neurol"},{"key":"2026091402101043000_97.10.923.30","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(83)90022-X"},{"key":"2026091402101043000_97.10.923.31","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-322640"},{"key":"2026091402101043000_97.10.923.32","doi-asserted-by":"crossref","unstructured":"Lennon VA . Serologic profile of myasthenia gravis and distinction from the Lambert-Eaton myasthenic syndrome. Neurology (ECronicon) 1997;48. doi:10.1212\/WNL.48.Suppl_5.23S","DOI":"10.1212\/WNL.48.Suppl_5.23S"},{"key":"2026091402101043000_97.10.923.33","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(86)90098-6"},{"key":"2026091402101043000_97.10.923.34","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1093\/clinchem\/39.10.2053","article-title":"Detection and characterization of blocking-type anti-acetylcholine receptor antibodies in sera from patients with myasthenia gravis","volume":"39","author":"Hara","year":"1993","journal-title":"Clin Chem"},{"key":"2026091402101043000_97.10.923.35","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198209233071301"},{"key":"2026091402101043000_97.10.923.36","doi-asserted-by":"publisher","DOI":"10.1126\/science.186.4158.55"},{"key":"2026091402101043000_97.10.923.37","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(83)80688-7"},{"key":"2026091402101043000_97.10.923.38","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(83)90096-5"},{"key":"2026091402101043000_97.10.923.39","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-302705"},{"key":"2026091402101043000_97.10.923.40","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-325511"},{"key":"2026091402101043000_97.10.923.41","first-page":"915","volume-title":"Using AChR Antibody Titres to Predict Treatment Responses in Myasthenia Gravis","volume":"92","author":"Vincent","year":"2021"},{"key":"2026091402101043000_97.10.923.42","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.43.7.590"},{"key":"2026091402101043000_97.10.923.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1987.tb51285.x"},{"key":"2026091402101043000_97.10.923.44","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2019.1690959","article-title":"Regulation of antibody-mediated complement-dependent cytotoxicity by modulating the intrinsic affinity and binding valency of IgG for target antigen","volume":"12","author":"Wang","year":"2020","journal-title":"MAbs"},{"key":"2026091402101043000_97.10.923.45","doi-asserted-by":"crossref","first-page":"103957","DOI":"10.1016\/j.ebiom.2022.103957","article-title":"Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19","volume":"78","author":"Pongracz","year":"2022","journal-title":"EBioMedicine"},{"key":"2026091402101043000_97.10.923.46","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.159.7.3372"},{"key":"2026091402101043000_97.10.923.47","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107949"},{"key":"2026091402101043000_97.10.923.48","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat Rev Dis Primers"}],"container-title":["Journal of Neurology, Neurosurgery &amp; Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jnnp-2025-338323","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:11:08Z","timestamp":1789377068000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnnp.bmj.com\/lookup\/doi\/10.1136\/jnnp-2025-338323"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,9,14]]},"published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1136\/jnnp-2025-338323"],"URL":"https:\/\/doi.org\/10.1136\/jnnp-2025-338323","relation":{},"ISSN":["0022-3050","1468-330X"],"issn-type":[{"value":"0022-3050","type":"print"},{"value":"1468-330X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,4]]}}}