{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:56:56Z","timestamp":1783648616663,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T00:00:00Z","timestamp":1573171200000},"content-version":"am","delay-in-days":258,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,2,23]],"date-time":"2019-02-23T00:00:00Z","timestamp":1550880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1705464"],"award-info":[{"award-number":["1705464"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["R01CA174385"],"award-info":[{"award-number":["R01CA174385"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP130570"],"award-info":[{"award-number":["RP130570"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP180466"],"award-info":[{"award-number":["RP180466"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005190","name":"Melanoma Research Alliance","doi-asserted-by":"publisher","award":["509800"],"award-info":[{"award-number":["509800"]}],"id":[{"id":"10.13039\/100005190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["CA160591"],"award-info":[{"award-number":["CA160591"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["E\u20101774"],"award-info":[{"award-number":["E\u20101774"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To obtain the comprehensive transcriptome profile of human citrulline\u2010specific B cells from patients with rheumatoid arthritis (\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Citrulline\u2010 and hemagglutinin\u2010specific B cells were sorted by flow cytometry using peptide\u2013streptavidin conjugates from the peripheral blood of\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      patients and healthy individuals. The transcriptome profile of the sorted cells was obtained by\n                      <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                      \u2010sequencing, and expression of key protein molecules was evaluated by aptamer\u2010based\n                      <jats:styled-content style=\"fixed-case\">SOMA<\/jats:styled-content>\n                      scan assay and flow cytometry. The ability of these proteins to effect differentiation of osteoclasts and proliferation and migration of synoviocytes was examined by in vitro functional assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Citrulline\u2010specific B cells, in comparison to citrulline\u2010negative B cells, from patients with\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      differentially expressed the interleukin\u201015 receptor \u03b1 (\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u201015R\u03b1) gene as well as genes related to protein citrullination and cyclic\n                      <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\n                      signaling. In analyses of an independent cohort of cyclic citrullinated peptide\u2013seropositive\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      patients, the expression of\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u201015R\u03b1 protein was enriched in citrulline\u2010specific\u00a0B cells from the patients\u2019 peripheral blood, and surprisingly, all B cells from\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      patients were capable of producing the epidermal growth factor ligand amphiregulin (\n                      <jats:styled-content style=\"fixed-case\">AREG<\/jats:styled-content>\n                      ). Production of\n                      <jats:styled-content style=\"fixed-case\">AREG<\/jats:styled-content>\n                      directly led to increased migration and proliferation of fibroblast\u2010like synoviocytes, and, in combination with anti\u2013citrullinated protein antibodies, led to the increased differentiation of osteoclasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      To the best of our knowledge, this is the first study to document the whole transcriptome profile of autoreactive B cells in any autoimmune disease. These data identify several genes and pathways that may be targeted by repurposing several\n                      <jats:styled-content style=\"fixed-case\">US<\/jats:styled-content>\n                      Food and Drug Administration\u2013approved drugs, and could serve as the foundation for the comparative assessment of B cell profiles in other autoimmune diseases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.40772","type":"journal-article","created":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T10:15:06Z","timestamp":1541672106000},"page":"529-541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Beyond Autoantibodies: Biologic Roles of Human Autoreactive B Cells in Rheumatoid Arthritis Revealed by RNA\u2010Sequencing"],"prefix":"10.1002","volume":"71","author":[{"given":"Ankit","family":"Mahendra","sequence":"first","affiliation":[{"name":"University of Houston  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Georgia Institute of Technology  Atlanta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaza","family":"Abnouf","sequence":"additional","affiliation":[{"name":"University of Houston  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay R. T.","family":"Adolacion","sequence":"additional","affiliation":[{"name":"University of Houston  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daechan","family":"Park","sequence":"additional","affiliation":[{"name":"Ajou University  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanam","family":"Soomro","sequence":"additional","affiliation":[{"name":"University of Houston  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Roszik","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center  Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Coarfa","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Romain","sequence":"additional","affiliation":[{"name":"University of Houston  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Wanzeck","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3785-1389","authenticated-orcid":false,"suffix":"Jr.","given":"S. Louis","family":"Bridges","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amita","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Sanjay Gandhi Postgraduate Institute of Medical Sciences  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Georgia Institute of Technology  Atlanta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep K.","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra","family":"Mohan","sequence":"additional","affiliation":[{"name":"University of Houston  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7524-8228","authenticated-orcid":false,"given":"Navin","family":"Varadarajan","sequence":"additional","affiliation":[{"name":"University of Houston  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24716"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203915"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-006-0049-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60975"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.141"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30596"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.062505"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.8.4710"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111675"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2094"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.169"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.2.1072"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39489"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-207182"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_7_17_1","first-page":"2579","article-title":"Visualizing data using t\u2010SNE","volume":"9","author":"Van der Maaten L","year":"2008","journal-title":"J Mach Learn Res"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx435"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.7.4067"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2090"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38207"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00934.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kem297"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-012-8346-7"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep29338"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5312.596"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2204"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.19.5734"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2462"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/830421"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi052646f"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2013.07.003"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v30.i5.50"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000832"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket350"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-015-0516-3"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/microarrays4030424"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.7.2840"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20810"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-7440-8"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.01.020"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-9255-5-5"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102693"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400562"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00859.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601912458284"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3237"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21249"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/jidsymp.2013.8"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/943156"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3161"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.01.005"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.49.9.665"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.40772","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40772","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.40772","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/art.40772","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40772","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T19:02:28Z","timestamp":1759950148000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.40772"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,23]]},"references-count":52,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1002\/art.40772"],"URL":"https:\/\/doi.org\/10.1002\/art.40772","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/144121","asserted-by":"object"}]},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,23]]},"assertion":[{"value":"2018-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}