AB0086 IL - 17 Levels with Vitamin D Repletion in Rheuamtoid Arthritis

Abstract

Background Increasing scientific evidence implicates a pathogenic role of Th17 cells and associated cytokines in rheumatoid arthritis (RA). Vitamin D may have suppressive effect on Th17 cells. In vitro studies show that vitamin D suppresses IL-17 production in stimulated PMBCs1 in patients with early RA. In a recent study2, serum 25(OH)D levels were inversely associated with IL-17 levels in RA patients. However, the effect of vitamin D repletion on IL-17 levels in RA remains untested. This is of clinical importance as correction of vitamin D deficiency may reduce IL-17 related inflammation in RA. Objectives Our goal was to compare serum IL-17 levels in vitamin D sufficient vs vitamin D deficient RA patients and to investigate the effect of vitamin D repletion on IL 17 levels in vitamin D deficient RA subjects. Methods Sera from RA patients (1987 ARA criteria) enrolled in a randomized controlled trial were used. 25(OH)D levels were measured using Diasorin radioimmunoassay. Vitamin D deficiency was classified as 25(OH)D level <30ng/ml. Vitamin D deficient patients were randomly assigned to either vitamin D therapy [50,000 IU ergocalciferol/week for 8 or 16 weeks until repletion [25(OH)D≥30 ng/ml] was achieved OR placebo for 16 weeks. Sera were collected and stored at -70 degrees every study visit. IL-17 was measured in both vitamin D sufficient (n=56) and deficient (n=83) patients at baseline. IL-17 was also measured in patients who completed vitamin D therapy and achieved repletion. We compared pre- and post-treatment IL-17 levels in this group. A commercially available Ruthenium based electro-chemoluminescence platform was used to measure IL-17 (lowest quantification level =0.2 pg/ml). Unpaired and paired students t-test and regression analyses were used. Results Participants (n=139) were mostly female (80%), white (79.1%) with a mean (SD) age of 53.4 (12.3) yrs, body mass index of 30.5 (6.9) m/kg2 and disease duration of 9.9 (9) yrs. Mean 25(OH)D levels were 28.3 (11.1)ng/mL (range 6.3 – 72.8 ng/ml). 83 participants (60%) patients had 25(OH)D levels <30 ng/ml and entered the RCT. 68 participants completed vitamin D repletion therapy. Mean increase in vitamin D in this group was 17.3 (12.9) ng/ml. In a cross-sectional analysis, no significant difference was noted in IL-17 levels at baseline between vitamin D sufficient and deficient groups (mean IL 17 0.71±1.27 pg/ml vs 0. 62±0.65 pg/ml respectively, p value=0.62). Using linear regression, baseline vitamin D sufficiency/deficiency was a non-significant predictor of IL -17 levels (beta= -0.04, p=0.622). After vitamin D repletion therapy, no differences were noted in IL-17 levels before and after repletion (IL-17 at baseline vs repletion, 0.61 (0.61) pg/ml vs 0.68 (0.93) pg/ml respectively, p=0.60). Conclusions These data suggest that IL-17 levels do not differ between vitamin D deficient and sufficient RA patients. Moreover, vitamin D repletion does not impact IL-17 levels. This is the first study to investigate the effect of vitamin D repletion therapy o...