{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:36:14Z","timestamp":1779881774195,"version":"3.53.1"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000568","name":"British Society for Rheumatology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000568","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010089","name":"JGW Patterson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","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":[[2025,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Endogenous retroelements (EREs) stimulate type 1 interferon (IFN\u2010I) production but have not been explored as potential interferonogenic triggers in rheumatoid arthritis (RA). We investigated ERE expression in early RA (eRA), a period in which IFN\u2010I levels are increased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ERE expression (long terminal repeat [LTR] 5, long interspersed nuclear element 1 [LINE\u20101], and short interspersed nuclear element [SINE]) in disease\u2010modifying treatment\u2010na\u00efve eRA whole\u2010blood and bulk synovial tissue samples was examined by reverse transcription\u2013polymerase chain reaction and NanoString alongside IFN\u2010\u03b1 activity. Circulating lymphocyte subsets, including B cell subsets, from patients with eRA and early psoriatic arthritis (ePsA) were flow cytometrically sorted and similarly examined. Existing established RA and osteoarthritis (OA) synovial single\u2010cell sequencing data were reinterrogated to identify repeat elements, and associations were explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was significant coexpression of all ERE classes and <jats:italic>IFNA<\/jats:italic> in eRA synovial tissue samples (n = 22, <jats:italic>P<\/jats:italic> &lt; 0.0001) and significant positive associations between whole\u2010blood LINE\u20101 expression (n = 56) and circulating IFN\u2010\u03b1 protein (<jats:italic>P<\/jats:italic> = 0.018) and anti\u2013cyclic citrullinated peptide (anti\u2010CCP) titers (<jats:italic>P<\/jats:italic> &lt; 0.0001). ERE expression was highest in circulating eRA B cells, particularly na\u00efve B cells compared with ePsA, with possible ERE regulation by SAM and HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1 transcription (SAMDH1) implicated and associations with <jats:italic>IFNA<\/jats:italic> again observed. Finally, in established RA synovium, LTRs, particularly human endogenous retroviral sequence K (HERVK), were most increased in RA compared with OA, in which, for all synovial subsets (monocytes, B cells, T cells, and fibroblasts), ERE expression associated with increased IFN\u2010I signaling (<jats:italic>P<\/jats:italic> &lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Peripheral blood and synovial ERE expression is examined for the first time in eRA, highlighting both a potential causal relationship between ERE and IFN\u2010I production and an intriguing association with anti\u2010CCP autoantibodies. This suggests EREs may contribute to RA pathophysiology with implications for future novel therapeutic strategies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.43083","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T21:50:32Z","timestamp":1734385832000},"page":"646-657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Endogenous Retroelement Activation is Implicated in Interferon\u2010\u03b1 Production and Anti\u2013Cyclic Citrullinated Peptide Autoantibody Generation in Early Rheumatoid Arthritis"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8529-3337","authenticated-orcid":false,"given":"Faye A. 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