{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:27:53Z","timestamp":1791912473411,"version":"4.3.4"},"reference-count":83,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,1,30]],"date-time":"2018-01-30T00:00:00Z","timestamp":1517270400000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U01NS084495"],"award-info":[{"award-number":["U01NS084495"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI114780"],"award-info":[{"award-number":["R01AI114780"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pathogenic autoantibodies to muscle\u2010specific tyrosine kinase (MuSK) can be found in patients with myasthenia gravis (MG) who do not have detectable antibodies to the acetylcholine receptor. Although the autoantibody\u2010mediated pathology is well understood, much remains to be learned about the cellular immunology that contributes to autoantibody production. To that end, our laboratory has investigated particular components associated with the cellular immunopathology of MuSK MG. First, we found that B cell tolerance defects contribute to the abnormal development of the naive repertoire, which indicates that dysregulation occurs before the production of autoantibodies. Second, both the naive and antigen\u2010experienced memory B cell repertoire, which we examined through the application of high\u2010throughput adaptive immune receptor repertoire sequencing, include abnormalities not found in healthy controls. This highlights a broad immune dysregulation. Third, using complementary approaches, including production of human monoclonal antibodies, we determined that circulating plasmablasts directly contribute to the production of MuSK\u2010specific autoantibodies in patients experiencing relapse following B cell depletion therapy. These collective findings contribute to defining a mechanistic model that describes MuSK MG immunopathogenesis.<\/jats:p>","DOI":"10.1111\/nyas.13535","type":"journal-article","created":{"date-parts":[[2018,1,30]],"date-time":"2018-01-30T13:14:00Z","timestamp":1517318040000},"page":"154-165","source":"Crossref","is-referenced-by-count":47,"title":["Mechanisms underlying B cell immune dysregulation and autoantibody production in MuSK myasthenia gravis"],"prefix":"10.1111","volume":"1412","author":[{"given":"Panos","family":"Stathopoulos","sequence":"first","affiliation":[{"name":"Department of Neurology Yale School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1474-310X","authenticated-orcid":false,"given":"Jason A. Vander","family":"Heiden","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elba","family":"Pascual\u2010Go\u00f1i","sequence":"additional","affiliation":[{"name":"Neurology Department Hospital de la Santa Creu i Sant Pau  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7056-419X","authenticated-orcid":false,"given":"Kevin C.","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,30]]},"reference":[{"key":"e_1_2_8_2_1","article-title":"B cells in the pathophysiology of myasthenia gravis","author":"Yi J.S.","year":"2017","journal-title":"Muscle Nerve"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.8206.1","article-title":"Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms","author":"Phillips W.D.","year":"2016","journal-title":"F1000Res"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.180.4088.871"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880171208"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22312"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws025"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2012.01.025"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21545"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2008.01.013"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2016.04.019"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080695"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2016.11.005"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197805182982004"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000077"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2013.09.006"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182407982"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2008.02399.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2008.04.039"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756285611411503"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21521"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2008.09.001"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086907"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042321"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042251"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68775"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.311"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062287"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.09.015"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61788"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI83840"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909775106"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700169"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26232"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3175"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008930"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601415"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11112"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94263"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-303664"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115723"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11181"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.236"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501843"},{"key":"e_1_2_8_45_1","first-page":"85","article-title":"Roles of plasmablasts and B cells in IgG4\u2010related disease: implications for therapy and early treatment outcomes","volume":"401","author":"Lanzillotta M.","year":"2017","journal-title":"Curr. Top. Microbiol. Immunol"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701132"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24185"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21802"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.4.1919"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1144603"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067752"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-341131"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010111125"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.26"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198906013202206"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(00)00158-4"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062930"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1508234"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005166"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000228225.23349.5d"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30070-3"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.172"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31822e9d66"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810457"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014070640"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2010.220475"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.22006"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1001\/archdermatol.2009.9"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2012.72"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60720-0"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.03.034"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205799"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205233"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1602678"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20479"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20411"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-006-0442-2"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2006.093567"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.197632"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1097\/CND.0b013e3181df2b3e"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1097\/CND.0b013e3181fcc109"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-013-6987-y"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24063"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.03.014"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnyas.13535","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nyas.13535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T10:15:34Z","timestamp":1694513734000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1111\/nyas.13535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":83,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1111\/nyas.13535"],"URL":"https:\/\/doi.org\/10.1111\/nyas.13535","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]}}}