title: Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy.
abstract: BACKGROUND
  The objective of this study was to investigate the effects of tumor necrosis factor (TNF)-α inhibitors on circulating T helper-type 17 (Th17) cells and Th17-related cytokines in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  The frequencies of circulating Th17 cells and serum levels of Th17-related cytokines were determined using flow cytometry analysis and ELISA, respectively, in 48 RA patients both before (baseline) and six months after anti-TNF-α therapy. Therapeutic response was evaluated using European League Against Rheumatism (EULAR) response criteria.
  
  
  RESULTS
  Significantly higher baseline frequencies of circulating Th17 cells and serum levels of interleukin (IL)-6, IL-17, IL-21, IL-23 and TNF-α were observed in active RA patients than in 12 healthy controls (all P < 0.001). After anti-TNF-α therapy, 36 patients (75%) were EULAR responders (20 good responders and 16 moderate responders) and 12 (25.0%) were non-responders. The mean levels of circulating Th17 cells and IL-17 significantly decreased (1.13% vs. 0.79%; 43.1 pg/ml vs. 27.8 pg/ml; respectively, both P < 0.001) in parallel with clinical remission in responders. Levels of IL-6, IL-21, IL-23 and TNF-α were significantly decreased after anti-TNF-α therapy in responders. In contrast, the mean levels of circulating Th17 cells and IL-17 significantly increased after anti-TNF-α therapy (2.94% vs. 4.23%; 92.1 pg/ml vs. 148.6 pg/ml; respectively, both P < 0.05) in non-responders. Logistic regression analysis identified a high baseline level of IL-17 as a significant predictor of poor therapeutic response.
  
  
  CONCLUSIONS
  The beneficial effect of anti-TNF-α therapy might involve a decrease in Th17-related cytokines in responders, whereas rising levels of circulating Th17-cells and IL-17 were observed in patients with an inadequate response to anti-TNF-α therapy.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, No, 160, Section 3, Taichung-Kang Road, Taichung, 407, Taiwan.
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chen
authors.forename: Hsin-Hua
authors.initials: HH
authors.lastname: Chen
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Hsieh
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
authors.forename: Joung-Liang
authors.initials: JL
authors.lastname: Lan
mesh_terms: D000068879:Adalimumab; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D002469:Cell Separation; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D020381:Interleukin-17 / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D058504:Th17 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D020381:Interleukin-17; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept