{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:39:03Z","timestamp":1787017143037,"version":"build-2736575974"},"reference-count":35,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"unspecified","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["R120782"],"award-info":[{"award-number":["R120782"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Arthritis CEntre","award":["22072"],"award-info":[{"award-number":["22072"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,2,7]]},"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Long-term outcomes in rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate (MTX) remains the first-line disease modifying therapy, however there are no biomarkers with which to identify those most likely to achieve remission. To address this unmet need we explored metabolic pathways involved in MTX mechanism of action within circulating CD4+T\u2009cells in a cohort of treatment naive patients with early RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Purified CD4+T\u2009cells were isolated from peripheral blood of 68 patients with early RA commencing MTX. The expression of a range of putative MTX metabolism and mechanism of action targets were explored by flow-cytometry and transcriptional analysis. From these data significant predictors of Disease Activity Score 28-C reactive protein (DAS28-CRP) remission (&lt;2.4 at 6 months) were determined by logistic regression (clinical; flow-cytometry data) and linear modelling (gene expression data).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Low baseline DAS28-CRP was associated with remission at 6 months (p=0.02). Expression of the ectonucleotidase CD39, involved in ATP-ADP conversion during adenosine synthesis, was higher on CD4+CD25\u2009High regulatory T cells at baseline in those achieving remission (molecules of equivalent fluorescence 1264 vs 847; p=0.007). Expression of other adenosine signalling elements in CD4+T\u2009cells were also upregulated at baseline in patients achieving remission:\n                      <jats:italic>AMPD1<\/jats:italic>\n                      (p&lt;0.001),\n                      <jats:italic>ADORA2b<\/jats:italic>\n                      (p=0.039) and\n                      <jats:italic>ADORA3<\/jats:italic>\n                      (p=0.047). When combined into a single predictive metric, a combination of these variables outperformed baseline DAS28-CRP in prediction of early remission (area under the curve 0.92 vs 0.67, p=0.001)\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Adenosine signalling is important in the achievement of early remission with MTX in RA and biomarkers of adenosine activity may hold utility for the stratification of therapy in early disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2023-003858","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T07:50:14Z","timestamp":1708156214000},"page":"e003858","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Adenosine metabolic signature in circulating CD4+ T cells predicts remission in rheumatoid arthritis"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3271-3596","authenticated-orcid":false,"given":"Philip M","family":"Brown","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK"},{"name":"National Institute of Health and Care Research (NIHR) Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle Upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E","family":"Anderson","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK"},{"name":"National Institute of Health and Care Research (NIHR) Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle Upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najib","family":"Naamane","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK"},{"name":"National Institute of Health and Care Research (NIHR) Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle Upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W","family":"Lendrem","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann W","family":"Morgan","sequence":"additional","affiliation":[{"name":"Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK"},{"name":"NIHR Leeds Biomedical Research Centre and NIHR Leeds Medtech and In Vitro Diagnostics Co-operative, Leeds Teaching Hospitals NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK"},{"name":"National Institute of Health and Care Research (NIHR) Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle Upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9909-8209","authenticated-orcid":false,"given":"Arthur G","family":"Pratt","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK"},{"name":"National Institute of Health and Care Research (NIHR) Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle 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