Mediators of apoptosis Fas and FasL predict disability progression in multiple sclerosis over a period of 10 years.
TNF-alpha, IL-12p35, IL-12p40, IL-4, IL-10, TGF-beta1, 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.:
Lopatinskaya
L
L
Division of Biomedical Research, TNO Quality of Life, P.O. Box 2215, 2301 CE, Leiden, The Netherlands.
Zwemmer
J
J
Uitdehaag
B
B
Lucas
K
K
Polman
C
C
Nagelkerken
L
L
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004185:Disability Evaluation; D053222:Fas Ligand Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D053222:Fas Ligand Protein; D012333:RNA, Messenger; D019014:fas Receptor