Retinol measurements and retinoid receptor gene expression in patients with multiple sclerosis

Abstract

Treatment with interferon (IFN)-β1a has been associated with decreased disease activity in patients with multiple sclerosis (MS). In several biological systems, type I IFNs and retinoids have been demonstrated to have synergistic effects. In these studies, we measured blood and cerebrospinal fluid (CSF) retinol levels and naïve and memory T-helper cell subset percentages in samples from a group of patients with MS. We also examined retinol receptor expression in peripheral blood cells from MS patients with or without a history of prior treatment with IFN-β1a. The mean plasma retinol level for untreated relapsing-remitting (RR) MS patients was lower than for patients with noninflammatory neurological disease. Among IFN-β1a-treated RR patients, mean levels were slightly higher than for RR patients not on treatment. Lower plasma retinol levels among the MS patients studied were associated with higher CSF retinol index measurements - a measure that was calculated to correct for nonspecific leakage of retinol from blood into CSF. For the MS samples examined, there was a borderline statistically significant direct correlation between CSF retinol index measurements and CSF memory T-helper cell percentages. Examination of peripheral blood from untreated RR patients for retinoid receptor mRNA expression revealed the expression of the retinoic acid receptor (RAR)-α, RAR-γ, and retinoic X receptor (RXR)-α receptor subtypes. For RR patients on IFN-β1a therapy, expression of the same RAR subtypes was noted as well as expression of RXR-βand RXR-γ. These studies suggest an association between plasma retinol levels and clinical disease activity in patients with MS and that treatment with IFN-β1a may be associated with activation of specific retinoid receptor subtypes.