{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:28:43Z","timestamp":1790206123906,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T00:00:00Z","timestamp":1591747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01NS090083\u201306"],"award-info":[{"award-number":["5R01NS090083\u201306"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Our aim in this study was to identify the prevalence and clinical characteristics of LRP4\/agrin\u2010antibody\u2013positive double\u2010seronegative myasthenia gravis (DNMG).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DNMG patients at 16 sites in the United States were tested for LRP4 and agrin antibodies, and the clinical data were collected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 181 DNMG patients, 27 (14.9%) were positive for either low\u2010density lipoprotein receptor\u2013related protein 4 (LRP4) or agrin antibodies. Twenty\u2010three DNMG patients (12.7%) were positive for both antibodies. More antibody\u2010positive patients presented with generalized symptoms (69%) compared with antibody\u2010negative patients (43%) (<jats:italic>P<\/jats:italic>\u2009\u2264\u2009.02). Antibody\u2010positive patients\u2019 maximum classification on the Myasthenia Gravis Foundation of America (MGFA) scale was significantly higher than that for antibody\u2010negative patients (<jats:italic>P<\/jats:italic>\u2009\u2264\u2009.005). Seventy percent of antibody\u2010positive patients were classified as MGFA class III, IV, or V compared with 39% of antibody\u2010negative patients. Most LRP4\u2010 and agrin\u2010antibody\u2013positive patients (24 of 27, 89%) developed generalized myathenia gravis (MG), but with standard MG treatment 81.5% (22 of 27) improved to MGFA class I or II during a mean follow\u2010up of 11\u2009years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Antibody\u2010positive patients had more severe clinical disease than antibody\u2010negative patients. Most DNMG patients responded to standard therapy regardless of antibody status.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.26985","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T04:40:17Z","timestamp":1591072817000},"page":"333-343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Clinical features of <scp>LRP4<\/scp>\/agrin\u2010antibody\u2013positive myasthenia gravis: A multicenter study"],"prefix":"10.1002","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6135-035X","authenticated-orcid":false,"given":"Michael H.","family":"Rivner","sequence":"first","affiliation":[{"name":"Department of Neurology Augusta University  Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandy M.","family":"Quarles","sequence":"additional","affiliation":[{"name":"Department of Neurology Augusta University  Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Xiu","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Case Western Reserve University  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Case Western Reserve University  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7136-8617","authenticated-orcid":false,"suffix":"Jr","given":"James F.","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Neurology University of North Carolina at Chapel Hill  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Corse","sequence":"additional","affiliation":[{"name":"Department of Neurology The Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazen M.","family":"Dimachkie","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Kansas  Kansas City Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlayne","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Texas Health Science Center at San Antonio  San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Neurology University of South Florida  Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Small","sequence":"additional","affiliation":[{"name":"Department of Neurology Allegheny General Hospital  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Lisak","sequence":"additional","affiliation":[{"name":"Department of Neurology Wayne State University  Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Belsh","sequence":"additional","affiliation":[{"name":"Department of Neurology Rutgers Robert Wood Johnson Medical School  New Brunswick New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikjae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale University  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Baute","sequence":"additional","affiliation":[{"name":"Department of Neurology Wake Forest University  Winston\u2010Salem North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Scelsa","sequence":"additional","affiliation":[{"name":"Department of Neurology Mount Sinai\u2010Beth Israel Hospital  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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