Background Interleukin (IL)-17 plays a pivotal role in Rheumatoid Arthritis (RA) pathogenesis, driving the T-helper (Th) response to the auto-reactivity and pro-inflammatory status (Th1-Th17 branch). Among cytokines involved in IL-17 cascade, IL-22 is produced by T-cells producing IL-17 (Th17) and allows the proliferation and survival of themselves. It has been described that IL-22 levels in RA are related to the clinical disease activity and to the presence of bone erosions. In our previous evaluation, we showed that costimulation blockade performed by Abatacept (ABA) is able to reduce circulating T-cells able to produce IL-17 after in vitro stimulation; the reduction of this subpopulation was directly related to the improvement of clinical disease activity (1).
Objectives The aim of this study is to investigate whether the reduction of Th17 cells after ABA treatment in RA may be influenced by variation of IL-22 serum levels.
Methods 30 patients (4 male, 26 female; median age: 53, IQR:44-60 years) treated with ABA for at least 6 months were enrolled. Disease activity and clinical response to the treatment were evaluated with DAS-28(CRP) and EULAR Response Criteria respectively. IL-17 production by T cells was evaluated by flow-cytometry, with intracytoplasmatic staining of PBMC stimulated for 6 hours with PMA-ionomycin, as previously reported (1); IL-22 serum levels were evaluated by ELISA (R&D System).
Results After 6 months of treatment 16 patients achieved the clinical remission. At baseline, 10 patients showed raised serum levels of IL-22 than the range of normality, provided by the manufacturers (>53.3 pg/ml), whereas 20 patients showed normal levels (≤53.3 pg/ml).
At baseline, no significant difference was observed in IL-22 levels between patients that achieved clinical remission and the others (24.6 (7.5-106.4) vs 42.7 (11.7-52.7)pg/ml; p: 0.15). After 6 months of treatment, a not significant reduction of IL-22 levels was seen in the total cohort of patients (from 38.3 (7.7-93.0) to 33.8 (11.1-74.8) pg/ml; p: 0.56). Patients that achieved clinical remission showed a significant lower probability of serum-conversion after 6 months of ABA treatment (from normal to high titer), than non-responders (0 vs 55%; p:0.01). The variation of IL-22 levels correlated with the modification of the number of circulating T-cells able to produce IL-17 after in vitro stimulation (p:0.002; r: 0.75). No correlation was seen between the variation of IL-22 titer and of DAS-28.
Conclusions IL-22 serum levels seem to be not modified by ABA treatment, whereas the reduction of IL-17 producing T-cells yet described is correlated to the modification of IL-22 titer. Further studies need to clarify the effects of ABA on IL-22.
Scarsi M, et al. Clin Exp Rheum 2014, in press.
Disclosure of Interest None declared
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