Perron, Hervé and Germi, Raphaëlle and Bernard, Corinne and García Montojo, Marta and Deluen, Cécile and Farinelli, Laurent and Faucard, Raphaël and Véas, Francisco and Stefas, Ilias and Fabriek, Babs O. and Van Horssen, Jack and Van der Valk, Paul and Gerdil, Claire and Mancuso, Roberta and Saresella, Marina and Clerici, Mario Salvatore and Marcel, Sébastien and Creange, Alain and Cavaretta, Rosella and Caputo, Domenico and Arru, Giannina and Morand, Patrice and Lang, Alois B. and Sotgiu, Stefano and Ruprecht, Klemens and Rieckmann, Peter and Villoslada, Pablo and Chofflon, Michel and Boucraut, José and Pelletier, Jean and Hartung, Hans Peter (2012) Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease. Multiple Sclerosis Journal, Vol. 18 (12), p. 1721-1736. eISSN 1477-0970. Article.
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Background: The envelope protein from multiple sclerosis (MS) associated retroviral element (MSRV), a member of the Human Endogenous Retroviral family ‘W’ (HERV-W), induces dysimmunity and inflammation.
Objective: The objective of this study was to confirm and specify the association between HERV-W/MSRV envelope (Env) expression and MS.
Methods: 103 MS, 199 healthy controls (HC) and controls with other neurological diseases (28), chronic infections (30) or autoimmunity (30) were analysed with an immunoassay detecting Env in serum. Env RNA or DNA copy numbers in peripheral blood mononuclear cells (PBMC) were determined by a quantitative polymerase chain reaction (PCR). Env was detected by immunohistology in the brains of patients with MS with three specific monoclonals.
Results: Env antigen was detected in a serum of 73% of patients with MS with similar prevalence in all clinical forms, and not in chronic infection, systemic lupus, most other neurological diseases and healthy donors (p<0.01). Cases with chronic inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were positive. RNA expression in PBMC and DNA copy numbers were significantly elevated in patients with MS versus HC (p<0.001). In patients with MS, DNA copy numbers were significantly increased in chronic progressive MS (secondary progressive MS vs relapsing–remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS –<0.02). Env protein was evidenced in macrophages within MS brain lesions with particular concentrations around vascular elements.
Conclusion: The association between MS disease and the MSRV-type HERV-W element now appears quite strong, as
evidenced ex-vivo from serum and PBMC with post-mortem confirmation in brain lesions. Chronic progressive MS, RRMS and clinically isolated syndrome show different ELISA (Enzyme-Linked Immunosorbent Assay) and/or PCR profiles suggestive of an increase with disease evolution, and amplicon sequencing confirms the association with particular HERV-W elements.
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