Metabolomic Networks Associated with Changes in Cytokine Expression Differ in Multiple Sclerosis Patients and Healthy Controls Following Vitamin D Supplementation (P5.297)

BACKGROUND: Evidence suggests multiple sclerosis (MS) patients have altered metabolomic profiles compared with healthy individuals. Whether these correlate with differences in cytokine expression is unknown. OBJECTIVE: To assess whether untargeted metabolic profiles of MS patients and healthy controls (HCs) are associated with the proportion of CD4+ T-cells producing interleukin-17 (IL-17) or interferon-gamma (IFNγ). METHODS: The study was conducted among participants in a 90-day 5000 IU/day vitamin D3 supplementation trial who had relapsing remitting MS or were HC. Participants were non-obese white females, aged 18-60 years, with 25-hydroxyvitamin D levels ≤30ng/mL and provided blood samples at baseline and at the end of study. Metabolomics analysis was performed by liquid/gas chromatography with mass-spectrometry at Metabolon Inc. Immunostaining and flow-cytometry were used to assess the proportion of CD4+ T-cells producing IL-17 or IFNγ at baseline and end-of-study for a subset of participants. We constructed weighted-correlation networks to summarize metabolic profiles and assessed the association between changes in modules and cytokine expression using generalized estimating equations adjusting for age, BMI and time-varying vitamin D status. RESULTS: A total of 30 individuals (MS: n=14; HC: n=16) were included in the present study. We observed differences between MS patients and HCs with respect to the magnitude of changes in CD4+ IFNγ+ T-cells associated with changes in a metabolite-module enriched in urea cycle, arginine and proline metabolism (P<0.01). We also observed differences in the magnitude of change in CD4+IL-17+ T-cells and changes in modules enriched in plasmalogens and sphingomyelin metabolites (both P<0.01). CONCLUSIONS: In this preliminary study, with respect to metabolites-networks, we observed differences in the magnitude of change between MS patients and HC in the proportion of CD4+ T-cells producing IL-17 or IFNγ. Whether these differences are a cause or consequence of underlying MS is not clear and analyses should be repeated in a larger study. Disclosure: Dr. Fitzgerald has nothing to disclose. Dr. Bhargava has nothing to disclose. Dr. Steele has nothing to disclose. Dr. Cassard has nothing to disclose. Dr. Waubant has received personal compensation for activities with Roche Diagnostics Corporation, Genzyme Corporation, and Novartis. Dr. Waubant has received research support from Roche Diagnostics Corporation, Biogen Idec, and Novartis. Dr. Peter A. Calabresi has received personal compensation for activities with Abbott and Vertex as a consultant. Dr. Calabresi has received research support from Novartis, MedImmune and Biogen. Dr. Mowry has received research support from Teva Pharmaceuticals and Biogen Idec.