{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:38:05Z","timestamp":1791110285569,"version":"4.1.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"43","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,10,26]]},"abstract":"<jats:p>\n                    The 8.1 haplotype of the HLA complex has been reproducibly associated with several autoimmune diseases and traits, notably with thymus hyperplasia in patients with acquired generalized myasthenia gravis, an autoantibody-mediated disease directed at the muscle acetylcholine receptor. However, the strong linkage disequilibrium across this haplotype has prevented the identification of the causative locus, termed MYAS1. Here, we localized MYAS1 to a 1.2-Mb genome segment by reconstructing haplotypes and assessing their transmission in 73 simplex families. This segment encompasses the class III and proximal class I regions, between the BAT3 and C3-2-11 markers, therefore unambiguously excluding the class II loci. In addition, a case-control study revealed a very strong association with a core haplotype in this same region following an additive model (\n                    <jats:italic>P<\/jats:italic>\n                    = 7 \u00d7 10\n                    <jats:sup>-11<\/jats:sup>\n                    , odds ratio 6.5 for one copy and 42 for two copies of the core haplotype). Finally, we showed that this region is associated with a marked increase in serum titers of anti-acetylcholine receptor autoantibodies (\n                    <jats:italic>P<\/jats:italic>\n                    = 8 \u00d7 10\n                    <jats:sup>-6<\/jats:sup>\n                    ). Remarkably, this effect was suppressed by a second locus in cis on the 8.1 haplotype and located toward the class II region. Altogether, these data demonstrate the highly significant but complex effects of the 8.1 haplotype on the phenotype of myasthenia gravis patients and might shed light on its role in other autoimmune diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0406756101","type":"journal-article","created":{"date-parts":[[2004,10,15]],"date-time":"2004-10-15T20:23:41Z","timestamp":1097871821000},"page":"15464-15469","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":85,"title":["Pleiotropic effects of the 8.1 HLA haplotype in patients with autoimmune myasthenia gravis and thymus hyperplasia"],"prefix":"10.1073","volume":"101","author":[{"given":"Claire","family":"Vandiedonck","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U580 and Institut de Recherche Necker Enfants Malades, 161 Rue de S\u00e8vres, 75743 Paris Cedex 15, France; Association Claude Bernard, Coll\u00e8ge de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 5, France; F\u00e9d\u00e9ration de Neurologie Mazarin, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 47-83 Boulevard de l'H\u00f4pital, 75651 Paris Cedex 13, France; Service de Neurologie, Hospices Civils-H\u00f4pitaux Universitaires de Strasbourg, 1 Place de l'H\u00f4pital, 67091..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Beaurain","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U580 and Institut de Recherche Necker Enfants Malades, 161 Rue de S\u00e8vres, 75743 Paris Cedex 15, France; Association Claude Bernard, Coll\u00e8ge de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 5, France; F\u00e9d\u00e9ration de Neurologie Mazarin, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 47-83 Boulevard de l'H\u00f4pital, 75651 Paris Cedex 13, France; Service de Neurologie, Hospices Civils-H\u00f4pitaux Universitaires de Strasbourg, 1 Place de l'H\u00f4pital, 67091..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Giraud","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U580 and Institut de Recherche Necker Enfants Malades, 161 Rue de S\u00e8vres, 75743 Paris Cedex 15, France; Association Claude Bernard, Coll\u00e8ge de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 5, France; F\u00e9d\u00e9ration de Neurologie Mazarin, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 47-83 Boulevard de l'H\u00f4pital, 75651 Paris Cedex 13, France; Service de Neurologie, Hospices Civils-H\u00f4pitaux Universitaires de Strasbourg, 1 Place de l'H\u00f4pital, 67091..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Hue-Beauvais","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U580 and Institut de Recherche Necker Enfants Malades, 161 Rue de S\u00e8vres, 75743 Paris Cedex 15, France; Association Claude Bernard, Coll\u00e8ge de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 5, France; F\u00e9d\u00e9ration de Neurologie Mazarin, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 47-83 Boulevard de l'H\u00f4pital, 75651 Paris Cedex 13, France; Service de Neurologie, Hospices Civils-H\u00f4pitaux Universitaires de Strasbourg, 1 Place de l'H\u00f4pital, 67091..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Eymard","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U580 and Institut de Recherche Necker Enfants Malades, 161 Rue de S\u00e8vres, 75743 Paris Cedex 15, France; Association Claude Bernard, Coll\u00e8ge de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 5, France; F\u00e9d\u00e9ration de Neurologie Mazarin, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 47-83 Boulevard de l'H\u00f4pital, 75651 Paris Cedex 13, France; Service de Neurologie, Hospices Civils-H\u00f4pitaux Universitaires de Strasbourg, 1 Place de l'H\u00f4pital, 67091..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Tranchant","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U580 and Institut de Recherche Necker Enfants Malades, 161 Rue de S\u00e8vres, 75743 Paris Cedex 15, France; Association Claude Bernard, Coll\u00e8ge de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 5, France; F\u00e9d\u00e9ration de Neurologie Mazarin, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 47-83 Boulevard de l'H\u00f4pital, 75651 Paris Cedex 13, France; Service de Neurologie, Hospices Civils-H\u00f4pitaux Universitaires de Strasbourg, 1 Place de l'H\u00f4pital, 67091..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gajdos","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U580 and Institut de Recherche Necker Enfants Malades, 161 Rue de S\u00e8vres, 75743 Paris Cedex 15, France; Association Claude Bernard, Coll\u00e8ge de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 5, France; F\u00e9d\u00e9ration de Neurologie Mazarin, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 47-83 Boulevard de l'H\u00f4pital, 75651 Paris Cedex 13, France; Service de Neurologie, Hospices Civils-H\u00f4pitaux Universitaires de Strasbourg, 1 Place de l'H\u00f4pital, 67091..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Dausset","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U580 and Institut de Recherche Necker Enfants Malades, 161 Rue de S\u00e8vres, 75743 Paris Cedex 15, France; Association Claude Bernard, Coll\u00e8ge de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 5, France; F\u00e9d\u00e9ration de Neurologie Mazarin, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 47-83 Boulevard de l'H\u00f4pital, 75651 Paris Cedex 13, France; Service de Neurologie, Hospices Civils-H\u00f4pitaux Universitaires de Strasbourg, 1 Place de l'H\u00f4pital, 67091..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri-Jean","family":"Garchon","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U580 and Institut de Recherche Necker Enfants Malades, 161 Rue de S\u00e8vres, 75743 Paris Cedex 15, France; Association Claude Bernard, Coll\u00e8ge de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 5, France; F\u00e9d\u00e9ration de Neurologie Mazarin, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 47-83 Boulevard de l'H\u00f4pital, 75651 Paris Cedex 13, France; Service de Neurologie, Hospices Civils-H\u00f4pitaux Universitaires de Strasbourg, 1 Place de l'H\u00f4pital, 67091..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,10,15]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6792704"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/44853"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.15.120181.001125"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1983.tb00707.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1999.tb01398.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410160502"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199406233302507"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)05186-2"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0901-777"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.180.4088.871"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0960-5428(94)00040-U"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/103.3.579"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(93)90105-2"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-8411(03)00095-7"},{"key":"e_1_3_2_15_2","first-page":"240","volume":"1","year":"1974","unstructured":"Fritze, D., Herrman, C., Jr., Naeim, F., Smith, G. S. & Walford, R. L. (1974) Lancet 1, 240-242.4130248","journal-title":"Lancet"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.9.1555"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00179791"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(99)00062-2"},{"key":"e_1_3_2_19_2","unstructured":"Shimosato Y. & Mukai K. (1997) Tumors of the Mediastinum (Armed Forces Institute of Pathology Washington DC)."},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","unstructured":"Rosai J. (1999) Histological Typing of Tumors of the Thymus (Springer Berlin) 2nd Ed.","DOI":"10.1007\/978-3-642-60157-6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.6.885"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/301904"},{"key":"e_1_3_2_23_2","first-page":"1323","volume":"58","year":"1996","unstructured":"Sobel, E. & Lange, K. (1996) Am. J. Hum. Genet. 58, 1323-1337.8651310","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1156"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/133.3.737"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1086\/319501"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/379378"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.10252"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00253-7"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg066"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(00)00227-5"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1086\/342407"},{"key":"e_1_3_2_33_2","first-page":"192","volume":"91","year":"1995","unstructured":"Christensen, P. B., Jensen, T. S., Tsiropoulos, I., Sorensen, T., Kjaer, M., Hojer-Pedersen, E., Rasmussen, M. J. & Lehfeldt, E. (1995) Acta Neurol. Scand. 91, 192-195.7793234","journal-title":"Acta Neurol. Scand."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5538.461"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5253.1289"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1397"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1086\/346067"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(00)00118-X"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.1997.0140"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364110"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.09.040191.002425"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.21.9717"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(02)00200-9"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1978.tb01347.x"},{"key":"e_1_3_2_45_2","unstructured":"Beisel K. & Rose N. (1983) in Autoimmmune Endocrine Disease ed. Davies T. (Wiley New York) pp. 41-58."},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198909143211103"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh036"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.8.4637"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0406756101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T22:28:29Z","timestamp":1650925709000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0406756101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10,15]]},"references-count":48,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2004,10,26]]}},"alternative-id":["10.1073\/pnas.0406756101"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0406756101","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,10,15]]},"assertion":[{"value":"2004-10-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}