title: Increased interleukin 21 (IL-21) and IL-23 are associated with increased disease activity and with radiographic status in patients with early rheumatoid arthritis.
abstract: OBJECTIVE
  To investigate the levels of the T helper (Th)17-related cytokines interleukin 17A (IL-17A), IL-21, and IL-23 and their association with disease activity in rheumatoid arthritis (RA).
  
  
  METHODS
  In a longitudinal sample set from patients with early RA (< 6 months; n = 40), we measured the plasma cytokine levels of IL-17A, IL-21, and IL-23 and analyzed for correlation with disease activity in 28 joints (Disease Activity Score 28-joint count; DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and total Sharp score (TSS). In a transverse sample set of patients with chronic RA (> 8 years), using paired peripheral blood mononuclear cells and synovial fluid mononuclear cells, we investigated the cellular expression of IL-17A, IL-21, and IL-23R.
  
  
  RESULTS
  Patients with early-stage RA had significantly increased plasma levels of IL-21 and IL-23, but not IL-17A, compared to patients with chronic RA and healthy volunteer controls. Plasma levels of IL-21 and IL-23 after 12 months of treatment correlated with DAS28 and ESR, but not to TSS. Changes in IL-23 plasma levels from time of diagnosis to 12 months correlated with change in DAS28 and with TSS scores at 2 years. The numbers of CD4+ T cells producing IL-21 were significantly increased in the synovial fluid of patients with chronic RA, with only marginal coexpression of IL-21 and IL-17A.
  
  
  CONCLUSIONS
  Our results show a significant association between plasma levels of IL-21 and IL-23 and disease activity in RA, supporting the hypothesis that IL-21 and IL-23 are important pathogenic factors of this disease.
authors.affiliation: Institute of Medical Microbiology and Immunology, Universityof Aarhus, Aarhus, Denmark.
authors.forename: Tue Kruse
authors.initials: TK
authors.lastname: Rasmussen
authors.forename: Thomas
authors.initials: T
authors.lastname: Andersen
authors.forename: Malene
authors.initials: M
authors.lastname: Hvid
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.forename: Kim
authors.initials: K
authors.lastname: Hørslev-Petersen
authors.forename: Kristian
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.forename: Christian Kanstrup
authors.initials: CK
authors.lastname: Holm
authors.forename: Bent
authors.initials: B
authors.lastname: Deleuran
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D020381:Interleukin-17 / Q000097:blood / Q000276:immunology; D053759:Interleukin-23 / Q000097:blood / Q000276:immunology; D007378:Interleukins / Q000097:blood / Q000276:immunology; D007596:Joints / Q000276:immunology / Q000473:pathology; D011859:Radiography; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D000098546:Interleukin-21