title: Increased plasma IL-17F levels in rheumatoid arthritis patients are responsive to methotrexate, anti-TNF, and T cell costimulatory modulation.
abstract: The aims of this study are to compare plasma levels of IL17A, A/F, and F biomarkers in RA patients versus controls, and to determine responsiveness to methotrexate (MTX), anti-TNFs, and abatacept. We selected plasma samples from RA cohorts consisting of a cross-sectional RA cohort (N = 78) not receiving DMARDs at the time of sampling, as well as from longitudinal drug start cohorts (N = 71 patients) with pre/post samples including anti-TNF, abatacept, and MTX-treated patients. We assayed IL-17A, IL-17F, and IL17-A/F using a highly sensitive immunoassay system. Plasma levels of IL-17A, IL-17A/F, and IL-17F were all significantly increased in RA versus controls. The difference was largest in IL-17F, with median IL-17F levels in RA patients being approximately 18-fold higher than controls (81 pg/mL in RA vs. 4.4 pg/mL in controls, p < 0.001). Among the forms of IL-17, only IL-17F was decreased after therapy in the MTX cohort (p = 0.006), abatacept cohort (p < 0.001), and anti-TNF cohorts (p = 0.02), whereas IL-17A and IL-17A/F were not significantly decreased for any of the three drug cohorts. Synovial fluid analysis demonstrated higher IL-17F levels in RA (p = 0.016) than healthy controls. These results suggest a specific role for IL-17F in human RA pathogenesis and as a therapeutic target.
authors.affiliation: Department of Rheumatology, New York University Hospital for Joint Diseases, 301 East 17th Street, suite 1410, New York, NY, 10003, USA, manishjain.rheum@gmail.com.
authors.forename: Manish
authors.initials: M
authors.lastname: Jain
authors.forename: Mukundan
authors.initials: M
authors.lastname: Attur
authors.forename: Vika
authors.initials: V
authors.lastname: Furer
authors.forename: John
authors.initials: J
authors.lastname: Todd
authors.forename: Renita
authors.initials: R
authors.lastname: Ramirez
authors.forename: Michael
authors.initials: M
authors.lastname: Lock
authors.forename: Quynh A
authors.initials: QA
authors.lastname: Lu
authors.forename: Steven B
authors.initials: SB
authors.lastname: Abramson
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Greenberg
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; C440021:IL17F protein, human; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate