{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:40:10Z","timestamp":1792633210234,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T00:00:00Z","timestamp":1584403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001922","name":"Efficacy and Mechanism Evaluation Programme","doi-asserted-by":"publisher","award":["11\/100\/76"],"award-info":[{"award-number":["11\/100\/76"]}],"id":[{"id":"10.13039\/501100001922","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["36661"],"award-info":[{"award-number":["36661"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K015346\/1"],"award-info":[{"award-number":["MR\/K015346\/1"]}],"id":[{"id":"10.13039\/501100000265","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":[[2020,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To define the relationship of synovial B cells to clinical phenotypes at different stages of disease evolution and drug exposure in 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                      Synovial biopsy specimens and demographic and clinical data were collected from 2\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      cohorts (n = 329), one of patients with untreated early\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      (n = 165) and one of patients with established\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      with an inadequate response to tumor necrosis factor inhibitors (\n                      <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\n                      i\u2010\n                      <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                      ; n = 164). Synovial tissue was subjected to hematoxylin and eosin and immunohistochemical staining and semiquantitative assessment for the degree of synovitis (on a scale of 0\u20139) and of\n                      <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                      20+ B cell infiltrate (on a scale of 0\u20134). B cell scores were validated by digital image analysis and B cell lineage\u2013specific transcript analysis (\n                      <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                      \u2010Seq) in the early\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      (n = 91) and\n                      <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\n                      i\u2010\n                      <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                      (n = 127) cohorts. Semiquantitative\n                      <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                      20 scores were used to classify patients as B cell rich (\u22652) or B cell poor (&lt;2).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Semiquantitative B cell scores correlated with digital image analysis quantitative measurements and B cell lineage\u2013specific transcripts. B cell\u2013rich synovitis was present in 35% of patients in the early\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      cohort and 47.7% of patients in the\n                      <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\n                      i\u2010\n                      <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                      cohort (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.025). B cell\u2013rich patients showed higher levels of disease activity and seropositivity for rheumatoid factor and anti\u2013citrullinated protein antibody in early\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      but not in established\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      , while significantly higher histologic synovitis scores in B cell\u2013rich patients were demonstrated in both cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We describe a robust semiquantitative histologic B cell score that closely replicates the quantification of B cells by digital or molecular analyses. Our findings indicate an ongoing B cell\u2013rich synovitis, which does not seem to be captured by standard clinimetric assessment, in a larger proportion of patients with established\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      than early\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.41184","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T05:01:50Z","timestamp":1575262910000},"page":"714-725","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["B Cell Synovitis and Clinical Phenotypes in Rheumatoid Arthritis: Relationship to Disease Stages and Drug Exposure"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-7521","authenticated-orcid":false,"given":"F.","family":"Rivellese","sequence":"first","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-9133","authenticated-orcid":false,"given":"F.","family":"Humby","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Bugatti","sequence":"additional","affiliation":[{"name":"IRCCS Policlinico San Matteo Foundation and University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3757-3999","authenticated-orcid":false,"given":"L.","family":"Fossati\u2010Jimack","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Barts Health NHS Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8019-556X","authenticated-orcid":false,"given":"D.","family":"Lucchesi","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Lliso\u2010Ribera","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Nerviani","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. E.","family":"Hands","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Giorli","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Frias","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Thorborn","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2769-0171","authenticated-orcid":false,"given":"E.","family":"Jaworska","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"John","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Goldmann","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9365-5345","authenticated-orcid":false,"given":"M. J.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Manzo","sequence":"additional","affiliation":[{"name":"IRCCS Policlinico San Matteo Foundation and University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Bombardieri","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Pitzalis","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the PEAC\u2010R4RA Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032534"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.rhu.0000111316.59676.db"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0060001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2497"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2011.153312"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60975"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204543"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23284"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.217"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32835fd8eb"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4555"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214539"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu163"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40218"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.1.785"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.139287"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23505"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204603"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2006.02508.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425830"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3519"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.091"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-483792"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13182"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-1-54"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.141199"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.036905"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/39.1.43"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.58.8.493"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.194"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215751"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez049"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22143"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1733"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.7.635"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40433"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.066704"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213418"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39235"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.029751"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40428"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.41184","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.41184","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.41184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T19:41:59Z","timestamp":1759952519000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.41184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,17]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1002\/art.41184"],"URL":"https:\/\/doi.org\/10.1002\/art.41184","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,17]]},"assertion":[{"value":"2019-06-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}