{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:58:34Z","timestamp":1791349114115,"version":"4.3.1"},"reference-count":22,"publisher":"Portland Press Ltd.","issue":"6","license":[{"start":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T00:00:00Z","timestamp":1564099200000},"content-version":"vor","delay-in-days":259,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,12,21]]},"abstract":"<jats:p>Myasthenia gravis (MG) is a rare prototypical autoimmune disorder caused by antibodies (Ab) against postsynaptic membrane proteins. Most reports have investigated the role of autoimmune regulator gene (Aire) in thymic tissue in machianism of MG initiation. So far, the expression of Aire in human peripheral blood cells (we call it circulating Aire expression in the following passage) has not been reported. Herein, we explore the expression of Aire in peripharal blood, circulating T-follicular helper (cTfh) and T-follicular regulatory (cTfr) cells in MG patients. In our research, we found that the acetylcholine receptor (AChR) Ab level is higher in generalized MG (GMG) than that in ocular MG (OMG). Compared with the control group (CG), lower expression of Aire was found in MG patients, especially in GMG. The ratio of Tfh\/Tfr was higher in GMG patients, and then in the OMG patients, and lowest in CG. All these differences above were statistically significant. Negative relation was discovered between expression of Aire in circulating blood and ratio of Tfh\/Tfr, so did it exist between Aire expression and the severity of MG. Meanwhile, positive relation was discovered between ratio of Tfh\/Tfr and the severity of MG. However, no significant relation was manifested in our study between the subset age of MG and Aire level. Overall, these findings imply circulating Aire might play a role in the imbalance of cTfh and cTfr cells and participate in the pathogenesis of MG.<\/jats:p>","DOI":"10.1042\/bsr20180096","type":"journal-article","created":{"date-parts":[[2018,5,17]],"date-time":"2018-05-17T16:55:20Z","timestamp":1526576120000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Decreased expression of circulating Aire and increased Tfh\/Tfr cells in myasthenia gravis patients"],"prefix":"10.1042","volume":"38","author":[{"given":"Sijia","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi 710038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi 710038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hyperbaric Oxygen, Navy General Hospital of Chinese People\u2019s Liberation Army, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi 710038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi 710038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi 710038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi 710038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,11,9]]},"reference":[{"key":"2021111619214985700_B1","doi-asserted-by":"publisher","first-page":"314","DOI":"10.21037\/jtd.2016.03.03","article-title":"Increased frequency of thymic T follicular helper cells in myasthenia gravis patients with thymoma","volume":"8","author":"Song","year":"2016","journal-title":"J. Thorac. Dis."},{"key":"2021111619214985700_B2","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1101\/gr.171645.113","article-title":"Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing and distribution of self-antigen expression in thymic epithelia","volume":"24","author":"Sansom","year":"2014","journal-title":"Genome Res."},{"key":"2021111619214985700_B3","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.immuni.2005.07.005","article-title":"The cellular mechanism of Aire control of T cell tolerance","volume":"23","author":"Anderson","year":"2005","journal-title":"Immunity"},{"key":"2021111619214985700_B4","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1084\/jem.20102327","article-title":"Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development","volume":"208","author":"Lei","year":"2011","journal-title":"J. Exp. Med."},{"key":"2021111619214985700_B5","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/nri2136","article-title":"A decade of AIRE","volume":"7","author":"Mathis","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"2021111619214985700_B6","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3109\/08916930903555935","article-title":"Thymoma and paraneoplastic myasthenia gravis","volume":"43","author":"Marx","year":"2010","journal-title":"Autoimmunity"},{"key":"2021111619214985700_B7","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.jocn.2017.02.049","article-title":"Rs3761389 polymorphism in autoimmune regulator (AIRE) gene is associated with susceptibility of myasthenia gravis in Chinese patients","volume":"40","author":"Zhang","year":"2017","journal-title":"J. Clin. Neurosci."},{"key":"2021111619214985700_B8","doi-asserted-by":"publisher","first-page":"326","DOI":"10.3389\/fimmu.2013.00326","article-title":"The many faces of Aire in central tolerance","volume":"4","author":"Laan","year":"2013","journal-title":"Front. Immunol."},{"key":"2021111619214985700_B9","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.immuni.2009.03.003","article-title":"Follicular helper T cells: lineage and location","volume":"30","author":"Fazilleau","year":"2009","journal-title":"Immunity"},{"key":"2021111619214985700_B10","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/S0165-5728(02)00038-3","article-title":"Thymic myoid cells and germinal center formation in myasthenia gravis; possible roles in pathogenesis","volume":"125","author":"Roxanis","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"2021111619214985700_B11","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2302\/kjm.20.69","article-title":"Thymoma and thymic germinal center","volume":"20","author":"Watanabe","year":"1971","journal-title":"Keio J. Med."},{"key":"2021111619214985700_B12","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1002\/ana.20340","article-title":"Selective loss of regulatory T cells in thymomas","volume":"56","author":"Str\u00f6bel","year":"2004","journal-title":"Ann. Neurol."},{"key":"2021111619214985700_B13","first-page":"447","article-title":"Peripheral Aire","volume":"342","author":"Dempsey","year":"2013","journal-title":"Science"},{"key":"2021111619214985700_B14","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.clim.2013.05.009","article-title":"ATRA alters humoral responses associated with amelioration of EAMG symptoms by balancing Tfh\/Tfr helper cell profiles","volume":"148","author":"Xie","year":"2013","journal-title":"Clin. Immunol."},{"key":"2021111619214985700_B15","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.neulet.2016.07.049","article-title":"Imbalance of circulating CD4+CXCR5+FOXP3+ Tfr-like cells and CD4+ CXCR5+ FOXP3- Tfh-like cells in myasthenia gravis","volume":"630","author":"Wen","year":"2016","journal-title":"Neurosci. Lett."},{"key":"2021111619214985700_B16","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1093\/intimm\/dxv079","article-title":"T follicular helper cells, T follicular regulatory cells and autoimmunity","volume":"28","author":"Zhu","year":"2016","journal-title":"Int. Immunol."},{"key":"2021111619214985700_B17","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.acthis.2013.10.009","article-title":"A preliminary study on the characterization of follicular helper T (Tfh) cells in rheumatoid arthritis synovium","volume":"116","author":"Chu","year":"2014","journal-title":"Acta Histochem."},{"key":"2021111619214985700_B18","doi-asserted-by":"publisher","first-page":"5767106","DOI":"10.1155\/2016\/5767106","article-title":"Follicular helper T cells in systemic lupus erythematosus: why should they be considered as interesting therapeutic targets?","volume":"2016","author":"Sawaf","year":"2016","journal-title":"J. Immunol. Res."},{"key":"2021111619214985700_B19","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1126\/science.1075958","article-title":"Projection of an immunological self shadow within the thymus by the Aire protein","volume":"298","author":"Anderson","year":"2002","journal-title":"Science"},{"key":"2021111619214985700_B20","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/j.1749-6632.2012.06843.x","article-title":"Experimental myasthenia gravis in Aire-deficient mice: a link between Aire and regulatory T cells","volume":"1275","author":"Aricha","year":"2012","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"2021111619214985700_B21","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1172\/JCI81894","article-title":"Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmue disease","volume":"126","author":"Dragin","year":"2016","journal-title":"J. Clin. Invest."},{"key":"2021111619214985700_B22","first-page":"17","article-title":"Aire-overexpressing dendritic cells induce peripheral CD4+ T cell tolerance","volume":"29","author":"Li","year":"2015","journal-title":"Int. J. Mol. Sci."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20180096\/809762\/bsr-2018-0096-t.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20180096\/809762\/bsr-2018-0096-t.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T20:16:45Z","timestamp":1637093805000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/38\/6\/BSR20180096\/98211\/Decreased-expression-of-circulating-Aire-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,9]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,12,21]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20180096","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,9]]},"article-number":"BSR20180096"}}