{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:31:53Z","timestamp":1793413913924,"version":"4.5.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"24","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI124084"],"award-info":[{"award-number":["R21 AI124084"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI 134834"],"award-info":[{"award-number":["R01 AI 134834"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["5K12 HD085848-03"],"award-info":[{"award-number":["5K12 HD085848-03"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["LR170055: W81XWH-18-1-06"],"award-info":[{"award-number":["LR170055: W81XWH-18-1-06"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1F32AI154797"],"award-info":[{"award-number":["1F32AI154797"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,6,15]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Pathogenic autoantibodies are a feature of systemic lupus erythematosus (SLE), of which 85% of patients are women. Multiple X chromosomes increase the risk for SLE, suggesting an important role for X-linked gene expression for the female sex bias. X-chromosome inactivation (XCI) regulates X-linked gene expression on the inactive X. This study examines XCI maintenance across multiple human B cell subsets from healthy individuals and SLE patients. Importantly, we found that both pediatric and adult SLE patient B cells have significant reductions with epigenetic modifications on the inactive X and aberrant X-linked gene expression. Our findings will be instrumental for future investigations of disease mechanisms underlying the female bias of SLE and abnormal autoantibody production in B cells.<\/jats:p>","DOI":"10.1073\/pnas.2024624118","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T15:37:33Z","timestamp":1623166653000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":119,"title":["The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3781-6463","authenticated-orcid":false,"given":"Sarah","family":"Pyfrom","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6589-8446","authenticated-orcid":false,"given":"Bam","family":"Paneru","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Knox","sequence":"additional","affiliation":[{"name":"Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8659-3227","authenticated-orcid":false,"given":"Michael P.","family":"Cancro","sequence":"additional","affiliation":[{"name":"Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6572-4291","authenticated-orcid":false,"given":"Sylvia","family":"Posso","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason, Seattle, WA 98101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9005-1885","authenticated-orcid":false,"given":"Jane H.","family":"Buckner","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason, Seattle, WA 98101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4992-3079","authenticated-orcid":false,"given":"Montserrat C.","family":"Anguera","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.10.6624"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.10.004"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3175"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-012-8365-8"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-330530"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2815"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1002\/art.39560","article-title":"X chromosome dose and sex bias in autoimmune diseases: Increased 47,XXX in systemic lupus erythematosus and Sjogren\u2019s syndrome","volume":"68","author":"Liu K.","year":"2016","unstructured":"K. Liu ., X chromosome dose and sex bias in autoimmune diseases: Increased 47,XXX in systemic lupus erythematosus and Sjogren\u2019s syndrome. Arthritis Rheumatol. 68, 1290\u20131300 (2016).","journal-title":"Arthritis Rheumatol."},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03440"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2011.11.012"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.124313"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118643"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/254245"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-017-3717-3"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124978"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603912103"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838138"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202195"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-397919"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600208"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/190372a0"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.42.110807.091711"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1084274"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00068-6"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu564"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.112680.110"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/351329a0"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/349038a0"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/379131a0"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03479"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-015-0053-7"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1520113113"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.126751"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03087"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03750-7"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007050"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.295907.117"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-091212-153530"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty203"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aap8855"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0419-9"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.03.025"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14443"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab2276"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.06.067"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.2.686"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.2"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24265"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2019.102357"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0728-8"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18589"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.633311"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aae0047"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2024624118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2024624118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T13:38:40Z","timestamp":1699105120000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2024624118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,8]]},"references-count":53,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2021,6,15]]}},"alternative-id":["10.1073\/pnas.2024624118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2024624118","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.11.25.399022","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,8]]},"assertion":[{"value":"2021-06-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2024624118"}}