{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:05:55Z","timestamp":1793736355275,"version":"4.6.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>We explored histological and transcriptomic profiles of paired synovial biopsies from rheumatoid arthritis (RA) patients, in order to assess homogeneity in synovial tissue at the individual level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Synovial biopsies were performed simultaneously in one small and one large joint per patient using needle-arthroscopy for the knee and ultrasound-guided biopsy for the hand or wrist. Synovium from individuals with osteoarthritis was used as controls. Paraffin-embedded samples were stained for CD3, CD20, and CD68. Total RNA was hybridized on high-density microarrays. <jats:italic>TCRB<\/jats:italic> variable sequences were obtained from synovial and blood RNA samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty paired biopsies from 10 RA patients with active disease were analyzed. Semi-quantification of histological markers showed a positive correlation for synovial hyperplasia, inflammatory infiltrates and CD3-positive T cells between pairs. Pairwise comparison of transcriptomic profiles showed similar expression of RA-related molecular pathways (TCR signaling, T cell costimulation and response to TNF\u03b1). T cells clonotypes were enriched in all but one joints compared to blood, regardless of the magnitude of T cell infiltration. Enriched clonotypes were shared between pairs (23\u2013100%), but this was less the case in pairs of joints displaying weaker T cell signatures and more pronounced germinal center-like transcriptomic profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Cellular and molecular alterations in RA synovitis are similar between small and large joints from the same patient. Interindividual differences in magnitude of T cell infiltrates and distribution of enriched T cell clonotypes support the concept of distinct synovial pathotypes in RA that are associated with systemic versus local antigen-driven activation of T cells.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2020.593083","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T07:37:29Z","timestamp":1606117049000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Paired Rheumatoid Arthritis Synovial Biopsies From Small and Large Joints Show Similar Global Transcriptomic Patterns With Enrichment of Private Specificity TCRB and TCR Signaling Pathways"],"prefix":"10.3389","volume":"11","author":[{"given":"Clement","family":"Triaille","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Vansteenkiste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Constant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Ambroise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"M\u00e9ric de Bellefon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Nzeusseu Toukap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Sokolova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Galant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Coulie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Carrasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Durez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard R.","family":"Lauwerys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1002\/art.40428","article-title":"Identification of three rheumatoid arthritis disease subtypes by machine learning integration of synovial histologic features and RNA sequencing data","volume":"70","author":"Orange","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1016\/j.celrep.2019.07.091","article-title":"Molecular portraits of early rheumatoid arthritis identify clinical and treatment response phenotypes","volume":"28","author":"Lewis","year":"2019","journal-title":"Cell Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1263-7","article-title":"Distinct fibroblast subsets drive inflammation and damage in arthritis","volume":"570","author":"Croft","year":"2019","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0378-1","article-title":"Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry","volume":"20","author":"Zhang","year":"2019","journal-title":"Nat Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"R57","DOI":"10.1186\/ar2678","article-title":"Gene expression profiling in the synovium identifies a predictive signature of absence of response to adalimumab therapy in rheumatoid arthritis","volume":"11","author":"Badot","year":"2009","journal-title":"Arthritis Res Ther"},{"key":"B6","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13075-016-0919-z","article-title":"Higher expression of TNF\u03b1-induced genes in the synovium of patients with early rheumatoid arthritis correlates with disease activity, and predicts absence of response to first line therapy","volume":"18","author":"De Groof","year":"2016","journal-title":"Arthritis Res Ther"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011310","article-title":"The gene expression profile in the synovium as a predictor of the clinical response to infliximab treatment in rheumatoid arthritis","volume":"5","author":"Lindberg","year":"2010","journal-title":"PloS One"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/art.40218","article-title":"Synovial immunophenotype and anti-citrullinated peptide antibodies in rheumatoid arthritis patients: relationship to treatment response and radiologic prognosis","volume":"69","author":"Orr","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"R90","DOI":"10.1186\/ar4555","article-title":"Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics","volume":"16","author":"Dennis","year":"2014","journal-title":"Arthritis Res Ther"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215751","article-title":"Synovial tissue signatures enhance clinical classification and prognostic\/treatment response algorithm in early inflammatory arthritis and predict requirement for subsequent biological therapy: results from the pathobiology of early arthritis cohort (PEAC)","volume":"78","author":"Lliso-Ribera","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/art.27415","article-title":"Synovial tissue heterogeneity in rheumatoid arthritis in relation to disease activity and biomarkers in peripheral blood","volume":"62","author":"van Baarsen","year":"2010","journal-title":"Arthritis Rheum"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2019.00046","article-title":"Synovial tissue: turning the page to precision medicine in arthritis","volume":"6","author":"Triaille","year":"2019","journal-title":"Front Med (Lausanne)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1002\/art.38202","article-title":"Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium","volume":"66","author":"Ducreux","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/art.10556","article-title":"Comparison of synovial tissues from the knee joints and the small joints of rheumatoid arthritis patients: implications for pathogenesis and evaluation of treatment","volume":"46","author":"Kraan","year":"2002","journal-title":"Arthritis Rheum"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800421","article-title":"In rheumatoid arthritis, synovitis at different inflammatory sites is dominated by shared but patient-specific T cell clones","volume":"201","author":"Musters","year":"2018","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.138461","article-title":"2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"69","author":"Aletaha","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364","article-title":"MIXCR : software for comprehensive adaptative immunity profiling","volume":"12","author":"Bolotin","year":"2015","journal-title":"Nat Methods"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14852","article-title":"Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions","volume":"8","author":"Frank-Bertoncelj","year":"2017","journal-title":"Nat Commun"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/art.22748","article-title":"Inflammation and ectopic lymphoid structures in rheumatoid arthritis synovial tissues dissected by genomics technology: Identification of the interleukin-7 signaling pathway in tissues with lymphoid neogenesis","volume":"56","author":"Timmer","year":"2007","journal-title":"Arthritis Rheum"},{"key":"B20","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s13075-015-0688-0","article-title":"Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis","volume":"17","author":"Ca\u00f1ete","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/art.23505","article-title":"Synovial lymphoid neogenesis does not define a specific clinical rheumatoid arthritis phenotype","volume":"58","author":"Thurlings","year":"2008","journal-title":"Arthritis Rheum"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.139287","article-title":"Presence of lymphocytes aggregates in the synovium of patients with early arthritis in relationship to diagnosis and outcome: is it a constant feature over time","volume":"70","author":"van de Sande","year":"2011","journal-title":"Ann Rheum Dis"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nature20810","article-title":"Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis","volume":"542","author":"Rao","year":"2017","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1371\/journal.pmed.0060001","article-title":"Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium","volume":"6","author":"Humby","year":"2009","journal-title":"PloS Med"},{"key":"B25","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1002\/art.27767","article-title":"V-region gene analysis of locally defined synovial B and plasma cells reveals selected B cell expansion and accumulation of plasma cell clones in rheumatoid arthritis","volume":"63","author":"Scheel","year":"2011","journal-title":"Arthritis Rheum"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208356","article-title":"Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells reveal frequent targeting of citrullinated histones of NETs","volume":"75","author":"Corsiero","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.089284","article-title":"Clinical significance of synovial lymphoid neogenesis and its reversal after anti-tumour necrosis factor alpha therapy in rheumatoid arthritis","volume":"68","author":"Ca\u00f1ete","year":"2009","journal-title":"Ann Rheum Dis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/s13075-018-1631-y","article-title":"Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue","volume":"20","author":"Donlin","year":"2018","journal-title":"Arthritis Res Ther"},{"key":"B29","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/s41467-017-02659-x","article-title":"Single-cell RNA-seq of rheumatoid arthritis synovial tissue using low-cost microfluidic instrumentation","volume":"9","author":"Stephenson","year":"2018","journal-title":"Nat Commun"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.593083\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T07:37:34Z","timestamp":1606117054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.593083\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":29,"alternative-id":["10.3389\/fimmu.2020.593083"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.593083","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]},"article-number":"593083"}}