Increased interleukin 21 (IL-21) and IL-23 are associated with increased disease activity and with radiographic status in patients with early rheumatoid arthritis.
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.
Rasmussen
Tue Kruse
TK
Institute of Medical Microbiology and Immunology, Universityof Aarhus, Aarhus, Denmark.
Andersen
Thomas
T
Hvid
Malene
M
Hetland
Merete Lund
ML
Hørslev-Petersen
Kim
K
Stengaard-Pedersen
Kristian
K
Holm
Christian Kanstrup
CK
Deleuran
Bent
B
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
D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D000098546:Interleukin-21