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

Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287, USA, wroyal{at}msm.edu

S Gartner

Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287, USA

C D Gajewski

Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287, USA

Treatment with interferon (IFN)-ß1a 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-ß1a. The mean plasma retinol level for untreated relapsing-remitting (RR) MS patients was lower than for patients with noninflammatory neurological disease. Among IFN-ß1a-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)-, RAR-, and retinoic X receptor (RXR)- receptor subtypes. For RR patients on IFN-ß1a therapy, expression of the same RAR subtypes was noted as well as expression of RXR-ßand RXR-. These studies suggest an association between plasma retinol levels and clinical disease activity in patients with MS and that treatment with IFN-ß1a may be associated with activation of specific retinoid receptor subtypes.

Key Words: interferon-ß 1a • multiple sclerosis • RAR • RXR • retinol • T-cell activation • vitamin A

Multiple Sclerosis, Vol. 8, No. 6, 452-458 (2002)
DOI: 10.1191/1352458502ms858oa


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