{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:54:00Z","timestamp":1793084040636,"version":"4.5.0"},"reference-count":46,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Centre for Medical Innovation Flanders"},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,10,1]]},"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To discover antibody biomarkers that can predict a lack of response to first-line therapy in rheumatoid arthritis (RA) patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Two RA cDNA phage display libraries were screened for novel antibodies in baseline RA sera from the Care in early RA (CareRA) trial, differentiating between patients who did or did not reach remission after first-line therapy (n=20\u2009each). Antibody reactivity to identified University Hasselt (UH)-RA antigens was validated in baseline samples from 136 additional CareRA participants. The novel antibodies\u2019 potential to predict failure to reach remission or low disease activity (LDA), according to the Disease Activity Score 28-joint C-reactive protein\/erythrocyte sedimentation rate (DAS28CRP\/ESR) and Clinical\/Simplified Disease Activity Index (CDAI\/SDAI), was studied by multivariate analyses. The presence of the antibody targets in RA synovial tissue and the fibroblast-like synoviocyte (FLS) cell line SW982 was determined by immunofluorescence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified antibodies to 41 novel antigens. Antibodies against any of three antigens, UH-RA.305\/318\/329, discriminated between RA patients not reaching week (w)8 DAS28CRP remission and those that did (36% vs 13%,p=0.0031). In all patients, anti-UH-RA.305\/318\/329 antibody reactivity was associated with failure to reach week 8 DAS28CRP and DAS28ESR remission (OR 3.63,p=0.0031; OR 2.92,p=0.016; respectively), SDAI\/CDAI sustained remission (OR 5.59,p=0.039 for both) and DAS28CRP and DAS28ESR sustained LDA (OR 3.7,p=0.009; OR 2.76,p=0.042; respectively). In rheumatoid factor\/anti-citrullinated protein antibody (RF\/ACPA) seronegative patients, these antibodies were strongly associated with failure to achieve week 8 DAS28CRP remission (OR 17.3,p=0.0029). Anti-UH-RA.305\/329 antibodies were shown to target FLS in RA synovial tissue and SW982 cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We identified three antibody biomarkers that are associated with failure to achieve remission\/LDA after first-line RA therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-004743","type":"journal-article","created":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T21:55:14Z","timestamp":1731880514000},"page":"e004743","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Fibroblast-like synoviocyte targeting antibodies are associated with failure to reach early and sustained remission or low disease activity after first-line therapy in rheumatoid arthritis"],"prefix":"10.1136","volume":"10","author":[{"given":"Patrick","family":"Vandormael","sequence":"first","affiliation":[{"name":"Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Hasselt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukayna","family":"Fadlallah","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Hasselt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Ruytinx","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Hasselt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Pues","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Hasselt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Sleurs","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Hasselt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jori","family":"Liesenborgs","sequence":"additional","affiliation":[{"name":"Expertise Centre for Digital Media Transnational University Limburg, UHasselt, Hasselt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Joly","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"Agten","sequence":"additional","affiliation":[{"name":"Faculty of Rehabilitation Sciences, REVAL-Rehabilitation Research Center, UHasselt, Hasselt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Vandenabeele","sequence":"additional","affiliation":[{"name":"Faculty of Rehabilitation Sciences, REVAL-Rehabilitation Research Center, UHasselt, Hasselt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Fraussen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Hasselt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0340-3580","authenticated-orcid":false,"given":"Patrick","family":"Verschueren","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium"},{"name":"Department of Development and Regeneration, Skeletal Biology and Engineering Research Centre, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4950-8724","authenticated-orcid":false,"given":"Veerle","family":"Somers","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Hasselt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,11,17]]},"reference":[{"key":"2025090313372303000_10.4.e004743.1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"2025090313372303000_10.4.e004743.2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/annrheumdis-2021-221935","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease- modifying antirheumatic drugs: 2022 update","volume":"0","author":"Smolen","year":"2022","journal-title":"Ann Rheum 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