{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:30:12Z","timestamp":1793115012600,"version":"4.5.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018748","name":"Argenx","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018748","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Myasthenia gravis (MG) is an autoimmune disorder primarily caused by autoantibodies against the acetylcholine receptor (AChR). Approximately 15% of MG patients, categorized as seronegative (snMG), lack detectable antibodies. Due to the snMG status, there may be a diagnostic delay. Moreover, there are limited data on treatment response in comparison to AChR-Ab+ patients. This study examines the burden of disease, treatment response, and quality of life of snMG patients in comparison to AChR-ab+ MG patients and healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A questionnaire-based survey was conducted collecting sociodemographic and clinical data including antibody status, therapy, treatment response, and self-rated disease severity along with standardized assessments such as MG-ADL (activities of daily living) and the Short Form Health (SF-36, generic Health-Related Quality of Life, HRQoL). HRQoL was evaluated through matched-pairs analyses. Participants from a general health survey served as the control group. Negative binomial regression was applied to evaluate the impact of antibody status on MG-ADL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to AChR-ab+ patients, snMG patients (<jats:italic>n<\/jats:italic> = 237) were younger at symptom onset [median age 42 (IQR 30.5\/53) vs. 51 (31\/64) years, <jats:italic>p<\/jats:italic> &amp;lt; 0.001] and had longer diagnostic delays. Complete stable remission was less frequent in snMG patients (15.9% vs. 27.8%, <jats:italic>p<\/jats:italic> &amp;lt; 0.001), and they reported higher disease severity (52.8% medium, 9.5% severe vs. 41.9% medium, 8.5% severe, <jats:italic>p<\/jats:italic> = 0.005). snMG patients had higher MG-ADL scores [median 5 (IQR 2\/9) vs. 3 (1\/6), <jats:italic>p<\/jats:italic> &amp;lt; 0.001] and more employment restrictions (64.4% vs. 49.3%, <jats:italic>p<\/jats:italic> &amp;lt; 0.001). Furthermore, compared to healthy controls, snMG patients showed worse outcomes in all domains of the SF-36.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The burden of disease in snMG patients is higher compared to AChR-ab+ MG due to delay in diagnosis, worse treatment response, and sociodemographic factors. These findings highlight the challenges patients and treating physicians face in snMG. There is a high need for earlier diagnosis, improved diagnostic tools, and inclusion of snMG patients in clinical trials to address their unique therapeutic challenges.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:uri>clinicaltrials.gov<\/jats:uri>, identifier NCT03979521. Registered 7 June 2019 (retrospectively registered).<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1555075","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T06:37:13Z","timestamp":1744094233000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["The burden of disease in seronegative myasthenia gravis: a patient-centered perspective"],"prefix":"10.3389","volume":"16","author":[{"given":"Sophie","family":"Lehnerer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Stegherr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Grittner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Gerischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Stascheit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meret","family":"Herdick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Doksani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Meisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.26.11.1054","article-title":"Antibody to acetylcholine receptor in myasthenia gravis","volume":"26","author":"Lindstrom","year":"1976","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/s12883-016-0756-3","article-title":"Response to treatment of myasthenia gravis according to clinical subtype","volume":"16","author":"Akaishi","year":"2016","journal-title":"BMC Neurol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/B978-0-12-823912-4.00026-8","article-title":"Myasthenia gravis-Pathophysiology, diagnosis, and treatment","volume":"200","author":"Tannemaat","year":"2024","journal-title":"Handb Clin Neurol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27331","article-title":"Gender differences in clinical outcomes in myasthenia gravis: A\u2009prospective cohort study","volume":"64","author":"Thomsen","year":"2021","journal-title":"Muscle Nerve"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27120","article-title":"The Duke myasthenia gravis clinic registry: I. 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