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

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Author: Lopatinskaya, L. · Zwemmer, J. · Uitdehaag, B. · Lucas, K. · Polman, C. · Nagelkerken, L.
Type:article
Date:2006
Institution: TNO Kwaliteit van Leven
Source:Multiple Sclerosis, 6, 12, 704-709
Identifier: 239675
doi: doi:10.1177/1352458506070826
Keywords: Biomedical Research · Apoptosis · Chemokines · Cytokines · EDSS · Fas · MS · chemokine receptor CCR3 · chemokine receptor CCR5 · chemokine receptor CXCR3 · Fas antigen · FAS ligand · interleukin 10 · interleukin 12p35 · interleukin 12p40 · interleukin 4 · messenger RNA · OKT 4 · osteopontin · transforming growth factor beta1 · tumor necrosis factor alpha · adult · apoptosis · article · clinical article · controlled study · correlation analysis · disability · disease association · disease course · Expanded Disability Status Scale · female · human · human cell · male · multiple sclerosis · pathophysiology · peripheral blood mononuclear cell · post hoc analysis · prediction · quantitative analysis · real time polymerase chain reaction · relapse · remission · Adult · Antibodies, Monoclonal · Antigens, CD95 · Apoptosis · Biological Markers · Chemokines · Cytokines · Disability Evaluation · Fas Ligand Protein · Female · Follow-Up Studies · Humans · Male · Middle Aged · Multiple Sclerosis, Chronic Progressive · Multiple Sclerosis, Relapsing-Remitting · Predictive Value of Tests · RNA, Messenger

Abstract

TNF-α, IL-12p35, IL-12p40, IL-4, IL-10, TGF-β1, 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. © 2006 SAGE Publications. Chemicals / CAS: osteopontin, 106441-73-0; Antibodies, Monoclonal; Antigens, CD95; Biological Markers; Chemokines; Cytokines; Fas Ligand Protein; RNA, Messenger