{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:56:50Z","timestamp":1789707410827,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,8,26]],"date-time":"2018-08-26T00:00:00Z","timestamp":1535241600000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow","award":["2015-111-IMP-EXP"],"award-info":[{"award-number":["2015-111-IMP-EXP"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      Nearly one\u2010third of patients with rheumatoid arthritis (RA) do not respond to Methotrexate (MTX), the first\u2010line therapy in RA. CD39, an ectonucleotidase highly expressed on regulatory T cells (Tregs), is responsible for production of adenosine, an important anti\u2010inflammatory mediator of MTX action. Higher expression of CD39 on Tregs improves their suppressive capacity. Therefore, we aimed to study the role of CD39\n                      <jats:sup>+<\/jats:sup>\n                      Treg frequency as a biomarker for MTX treatment response in RA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients with active RA who were naive to disease\u2010modifying anti\u2010rheumatic drugs were enrolled. Frequencies of CD39\n                      <jats:sup>+<\/jats:sup>\n                      Tregs (CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      FoxP3\n                      <jats:sup>+<\/jats:sup>\n                      CD39\n                      <jats:sup>+<\/jats:sup>\n                      cells) and CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      CD39\n                      <jats:sup>+<\/jats:sup>\n                      cells were determined by flow cytometry in peripheral blood before the start of therapy. After 4\u00a0months of MTX monotherapy, patients were classified into responders (European League Against Rheumatism [EULAR] good\/moderate response) and non\u2010responders (EULAR no response). All samples were genotyped for single nucleotide polymorphisms (SNPs) rs11188513 and rs7071836 in the\n                      <jats:italic>ENTPD1<\/jats:italic>\n                      (CD39) gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After 4\u00a0months of MTX monotherapy, 54 patients were classified as responders and 16 as non\u2010responders. The baseline CD39\n                      <jats:sup>+<\/jats:sup>\n                      Treg and CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      CD39\n                      <jats:sup>+<\/jats:sup>\n                      cell frequencies were significantly higher in the responder group as compared with the non\u2010responder group (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      &lt;\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.05 and\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      &lt;\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.01, respectively). AA genotype at SNP rs7071836 was associated with poor response to MTX (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      &lt;\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.05; odds ratio\u00a0=\u00a05.67; 95% CI\u00a0=\u00a01.12\u201328.75).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Higher frequencies of CD39\n                      <jats:sup>+<\/jats:sup>\n                      Tregs and CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      CD39\n                      <jats:sup>+<\/jats:sup>\n                      cells in the peripheral blood are associated with response to MTX in RA and hence, these could be considered as potential biomarkers for prediction of response to MTX treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1756-185x.13333","type":"journal-article","created":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T19:07:40Z","timestamp":1535569660000},"page":"1548-1556","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["CD39 positive regulatory T cell frequency as a biomarker of treatment response to methotrexate in rheumatoid arthritis"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2089-027X","authenticated-orcid":false,"given":"Vikas","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shobhita","family":"Katiyar","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7921-4199","authenticated-orcid":false,"given":"Ramnath","family":"Misra","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-5186","authenticated-orcid":false,"given":"Amita","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar578"},{"key":"e_1_2_8_3_1","first-page":"1423","article-title":"Consensus recommendations for the assessment and treatment of rheumatoid arthritis","volume":"28","author":"Wolfe F","year":"2001","journal-title":"J Rheumatol"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21641"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh199"},{"key":"e_1_2_8_6_1","first-page":"2521","article-title":"Contemporary disease modifying antirheumatic drugs (DMARD) in patients with recent onset rheumatoid arthritis in a US private practice: methotrexate as the anchor drug in 90% and new DMARD in 30% of patients","volume":"29","author":"Sokka T","year":"2002","journal-title":"J Rheumatol"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22783"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780351003"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/39.9.975"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780371013"},{"key":"e_1_2_8_11_1","first-page":"1631","article-title":"Effectiveness profiles and dose dependent retention of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. 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