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This pilot study systematically characterised treatment-specific effects of baricitinib, tofacitinib, and TNFi upon molecular signatures in RA patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Seventy-five patients with RA were enrolled across two prospective cohorts: an initial inception cohort treated with tofacitinib (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200915) and a subsequent confirmatory cohort treated with baricitinib or TNFi (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200960; baricitinib\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200929, TNFi\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200931), along with 17 and 33 healthy donors (HD)serving as controls for each cohort, respectively. mRNA expression of SOCS1, SOCS2, SOCS3, CIS1, and the immunoproteasome subunit \u03b22i was assessed in peripheral blood mononuclear cells by real-time PCR. SOCS2 protein levels were measured by ELISA, and serum IL-6 levels were evaluated in the baricitinib\/TNFi cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Responder rates were comparable across all three treatment groups at both time points. JAK inhibition was associated with a distinct SOCS suppression signature: SOCS2 mRNA declined progressively under both baricitinib and tofacitinib but not under TNFi blockade. SOCS1 and SOCS3 mRNA normalized under baricitinib over time, while SOCS3 elevation persisted throughout the observation period under TNFi. CIS1 was selectively suppressed under baricitinib. Partial discordance between SOCS2 mRNA and protein levels suggested post-transcriptional regulation. Baseline SOCS3 expression was significantly higher in baricitinib non-responders than responders, and early SOCS3 decline at 2\u00a0weeks distinguished TNFi responders from non-responders. Proteasomal \u03b22i mRNA was relatively upregulated under tofacitinib and TNFi but not under baricitinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>JAK inhibition drives a treatment-specific suppression of SOCS family members not observed under TNFi, reflecting differential remodelling of cytokine feedback networks. Baseline and early SOCS3 dynamics emerge as candidate biomarkers of treatment response. These findings may inform future efforts to personalise treatment selection in RA and warrant validation in larger, randomised cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-026-03895-7","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:43:16Z","timestamp":1789450996000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential regulation of SOCS signalling and immunoproteasome pathways by JAK inhibitors and TNF inhibitors in rheumatoid arthritis"],"prefix":"10.1186","volume":"28","author":[{"given":"Khetam","family":"Ghannam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linh Nguyen","family":"My","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Behrendt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Brunner-Weinzierl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Lux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Bertrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Wille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Gl\u00e4\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Heinemann-Dammann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Borucki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Feist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"issue":"2","key":"3895_CR1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/nrrheum.2013.168","volume":"10","author":"GR Burmester","year":"2014","unstructured":"Burmester GR, Feist E, Dorner T. 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