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Mediators of apoptosis Fas and FasL predict disability progression in multiple sclerosis over a period of 10 years

Division of Biomedical Research, TNO Quality of Life, P.O. Box 2215, 2301 CE, Leiden, The Netherlands, Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

J Zwemmer

Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

B Uitdehaag

Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

K Lucas

Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

C Polman

Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

L Nagelkerken

Division of Biomedical Research, TNO Quality of Life, P.O. Box 2215, 2301 CE, Leiden, The Netherlands, am.nagelkerken{at}pg.tno.nl

TNF-, IL-12p35, IL-12p40, IL-4, IL-10, TGF-ß1, CCR3, CXCR3, CCR5, Fas and FasL mRNA levels in PBMC of 25 multiple sclerosis (MS) patients were quantified at baseline by real-time PCR according to a post-hoc study design. The baseline values of the different markers were analysed with respect to their correlation with the increase in disability over a period of 10 years. High levels of Fas mRNA were associated with a favourable disease course in relapsing-remitting (RR) MS (R² = 0.74, P = 0.0001, n = 13), as measured by the Expanded Disability Status Scale (EDSS); high levels of FasL mRNA were associated with relatively mild disease progression (R² = 0.86, P = 0.0001, n = 12) in secondary progressive (SP) MS. These findings suggest that Fas-mediated apoptosis plays a major role in the mechanism underlying long-term disease progression in MS.

Key Words: apoptosis • chemokines • cytokines • EDSS • Fas • MS

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