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However, the relationship of TL1A to disease duration, activity, and response to anti-TNF and other therapies in RA is not clear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured soluble TL1A in synovial fluid (SF), serum, or plasma from RA first-degree relatives (FDRs) and in early RA and established disease. We measured the effects of anti-TNF and methotrexate (MTX) therapy on circulating TL1A from multiple independent RA treatment trials. We also determined the ability of a blocking anti-TL1A antibody to inhibit clinical disease and articular bone destruction in the murine collagen-induced arthritis (CIA) model of human RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Soluble TL1A was specifically elevated in the blood and SF of patients with RA compared to patients with other diseases and was elevated early in disease and in at-risk anti-cyclic citrullinated peptide (CCP) (+) first-degree relatives (FDRs). Therapeutic TNF inhibition reduced serum TL1A in both responders and non-responders, whereas TL1A declined following MTX treatment only in responders. In murine CIA, TL1A blockade was clinically efficacious and reduced bone erosions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TL1A is specifically elevated in RA from early in the disease course and in at-risk FDRs. The decline in TL1A after TNF blockade suggests that TL1A levels may be a useful biomarker for TNF activity in RA. These results support the further investigation of the relationship between TL1A and TNF and TL1A blockade as a potential therapeutic strategy in RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-020-02198-9","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T02:02:39Z","timestamp":1588816959000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Circulating TNF-like protein 1A (TL1A) is elevated early in rheumatoid arthritis and depends on TNF"],"prefix":"10.1186","volume":"22","author":[{"given":"Yun-Jeong","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Ah.","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Meylan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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All subjects provided informed consent and sample collection and sharing was approved by the local IRB. All authors provided input on the paper and consent for publication.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Chris D. Ward and Thi-Sau Migone were employees of Human Genome Sciences and owners of HGSI stock. Sarah Lamberth and David Lee are employees of Janssen Pharmaceuticals and own stock. V. Michael Holers and Kevin D. Deane are co-holders of a Stanford University patent on use of biomarkers to predict RA development. Richard Siegel, Yun-Jeong Song, and Fran\u00e7oise Meylan hold a patent on anti-TL1A antibodies. Richard Siegel has been an employee of Novartis Institutes of Biomedical Research since 2018 and owns Novartis stock. The remaining authors declared no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"106"}}