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Biological responsiveness to first injections of interferon-beta in patients with multiple sclerosis
Authors:Gilli F  Marnetto F  Caldano M  Sala A  Malucchi S  Di Sapio A  Capobianco M  Bertolotto A
Affiliation:

aLaboratoire d'Immunochimie, CEA/ INSERM-U548, 17 rue des Martyrs 38054 Grenoble, France

bLaboratorio di Biologia, Don C. Gnocchi Foundation, IRCCS, Via Capecelatro, 66, 20148 Milan, Italy

cMultiple Sclerosis dpt, Don C. Gnocchi Foundation, IRCCS, Via Capecelatro, 66, 20148 Milan, Italy

dService de Neurologie, Hôpital Henri Mondor, 51, Av Mar de Lattre de Tassigny 94000 Créteil, France

eDépartement des Immunoessais, bioMérieux, Chemin de l'Orme 69280 Marcy l'Etoile, France

Abstract:
MSRV is a retroviral element previously isolated in cell cultures from patients with multiple sclerosis. It is part of a new multi-copy endogenous retrovirus family named HERV-W and displays pro-inflammatory properties both in vitro in human PBMC cultures and in vivo in a humanized SCID mice model. In the present study, we have evaluated potential links between the pro-inflammatory properties of MSRV envelope protein and MS disease. Thus, cytokine productions mediated by the surface unit of MSRV envelope protein were evaluated in PBMC of MS patients and compared with healthy controls. Divergent reactivity to ENV-SU between MS and control PBMC was observed and was reflected by a significant increase of IFN-γ, IL-6 and IL-12p40 production by the tested MS population. Interestingly, the overproduction of IL-6 and IL-12p40 was found to correlate with disease severity (EDSS) in most patients. Altogether our data suggest that MSRV envelope protein may induce an abnormal cytokine secretion, thus contributing to the inflammatory process in MS.
Keywords:Multiple sclerosis   Endogenous retrovirus   Inflammation   Cytokines   Th1/Th2   HERV-W   MSRV
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