Cytokine Profiles Across DR2 Haplotype and Vitamin D Status in the Intermountain Multiple Sclerosis Project
Objectives: To investigate the relationship between DR2 haplotype, vitamin D status, and cytokine expression in MS in the Intermountain MS Project.
Methods: The Intermountain MS Project is a cohort study intended to identify biomarkers and genes in MS. Baseline patient serum samples were analyzed to: quantify concentrations of pro- and anti-inflammatory cytokines via Multiplexed Cytokine Assay, obtain DR2 haplotype information, and determine seasonally adjusted vitamin D concentrations.
Results: We report clinical characteristics of MS patients (n=797) and concentrations of pro- and anti-inflammatory cytokines stratified by DR2 haplotype and vitamin D status (normal versus insufficient/deficient). MS patients who were vitamin D insufficient or deficient were found to have statistically significantly higher levels of CD40-ligand, IL-1-beta, IL-2-receptor, and IL-12, and lower levels of IFN-gamma, IL-4, and IL-13 compared to those with normal vitamin D level. No cytokine expression was found to be statistically significantly different between DR2 positive versus negative patients. IL-12 and IL-13 expression were significantly decreased in DR2-positive patients who were vitamin D insufficient/deficient compared to normal (p = 0.022 and 0.0002, respectively), but this difference did not exist among DR2-negative patients (p = 0.055 and 0.510, respectively).
Conclusions: This study presents further analysis of the potential mechanism for a gene-environment interaction in MS; namely, the differential expression of IL-12 and Il-13 among DR2-positive patients who were vitamin D insufficient or deficient. The underlying immunology and potential implications of these results will be discussed.