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Response to TNF-\u03b1 inhibition may reflect the evolution of rheumatoid inflammation through fluctuating stages of TNF-\u03b1 dependence. Our aim was to assess plasma concentrations of Th-17-related cytokines and the presence of circulating effector T-cells to identify predictors of response to TNF-\u03b1 inhibitors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Ninety-three people with RA were seen prior to and 4\u20136 months after commencing etanercept or adalimumab. Plasma concentrations of Th17-related cytokines, circulating effector T-cells, their production of relevant transcription factors and intracellular cytokines were measured at baseline. EULAR response criteria were used to define poor (\u0394DAS28 \u2264 1.2 and\/or DAS28 &gt; 3.2) and good (\u0394DAS28 &gt; 1.2 and DAS28 \u2264 3.2) responders. Multivariate logistic regression was used to identify predictors of response.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Participants with plasma IL-23 present at baseline were more likely to be poor responders [15\/20 (75%) of IL-23<jats:sup>+<\/jats:sup> versus 36\/73 (49.3%) of IL-23<jats:sup>\u2212<\/jats:sup>; <jats:italic>p<\/jats:italic> = 0.041]. While frequencies of Th1, Th17, ex-Th17 and T<jats:sub>reg<\/jats:sub> cell populations were similar between good and poor responders to anti-TNF therapy, IL-17A<jats:sup>+<\/jats:sup>IFN\u03b3<jats:sup>+<\/jats:sup> ex-Th17 cells were more prevalent in good responders (0.83% of ex-T<jats:sub>H<\/jats:sub>17 cells) compared to poor responders (0.24% of ex-Th17 cells), <jats:italic>p<\/jats:italic> = 0.023. Both plasma IL-23 cytokine status (<jats:italic>OR<\/jats:italic> = 0.17 (95% <jats:italic>CI<\/jats:italic> 0.04\u20130.73)) and IL-17A<jats:sup>+<\/jats:sup>IFN\u03b3<jats:sup>+<\/jats:sup> ex-Th17 cell frequency (<jats:italic>OR<\/jats:italic> = 1.64 (95% <jats:italic>CI<\/jats:italic> 1.06 to 2.54)) were independently associated with a good response to anti-TNF therapy. Receiver operator characteristic (ROC) analysis, including both parameters, demonstrated an area under the ROC curve (AUC) of 0.70 (95% <jats:italic>CI<\/jats:italic> 0.60\u20130.82; <jats:italic>p<\/jats:italic> = 0.001).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Plasma IL-23 and circulating IL-17A<jats:sup>+<\/jats:sup>IFN\u03b3<jats:sup>+<\/jats:sup> ex-Th17 cells are independently associated with response to anti-TNF therapy. In combination, plasma IL-23 and circulating IL-17A<jats:sup>+<\/jats:sup>IFN\u03b3<jats:sup>+<\/jats:sup> ex-Th17 cells provide additive value to the prediction of response to anti-TNF therapy in RA.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-022-02748-3","type":"journal-article","created":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T09:02:53Z","timestamp":1645866173000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Plasma interleukin-23 and circulating IL-17A+IFN\u03b3+ ex-Th17 cells predict opposing outcomes of anti-TNF therapy in rheumatoid arthritis"],"prefix":"10.1186","volume":"24","author":[{"given":"Melanie J.","family":"Millier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh C.","family":"Fanning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Frampton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa K.","family":"Stamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6972-1242","authenticated-orcid":false,"given":"Paul A.","family":"Hessian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,26]]},"reference":[{"key":"2748_CR1","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/j.mayocp.2017.05.009","volume":"92","author":"CA Wijbrandts","year":"2017","unstructured":"Wijbrandts CA, Tak PP. 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