Although Epstein-Barr virus (EBV) has recently received increasingly attention as a potential causative infectious agent in Multiple Sclerosis (MS), the significance of EBV-specific humoral immune response in MS still remains to be clarified. The aim of our study was to investigate CSF and serum levels and the presence of an intrathecal synthesis of anti-EBV IgG in MS and controls. We measured by ELISA technique cerebrospinal fluid (CSF) and serum levels of anti-EBV IgG in 100 relapsing-remitting (RR) MS patients, grouped according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity, in 109 patients with other inflammatory neurological disorders (OIND) and in 87 patients with non-inflammatory neurological disorders (NIND). Anti-EBV nuclear antigen-1 (EBNA-1) and anti viral capsid antigen (VCA) IgG levels were expressed as arbitrary units and quantitative intrathecal synthesis of anti-EBNA-1 and anti-VCA IgG was determined by Antibody Index (AI). The presence of EBV-specific CSF oligoclonal IgG bands (OCB) was assessed in MS patients by antigen-specific immunoblotting. CSF concentrations were higher in OIND than in MS (p < 0.0001) and NIND (p < 0.01) for anti-VCA IgG, and in MS than in NIND (p < 0.01) and in OIND than in NIND (p < 0.05) for anti-EBNA-1 IgG. Serum levels of anti-EBNA-1 IgG were more elevated in in MS than in OIND and NIND (p < 0.0001). Serum titers of anti-EBNA-1 IgG were inversely (p < 0.001) correlated with EDSS. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a small proportion of MS and controls (range from 1.1 to 6.4%). EBV-specific CSF-restricted OCB were detected in 25/100 (25%) MS patients. Serum levels of anti-VCA IgG were greater in MS patients without than in those with EBV-specific CSF OCB. These findings argue against a direct pathogenetic role of EBV-targeted humoral immune response in MS. However, an intrathecal release of EBV-specific oligoclonal IgG can occur in a subset of patients with MS in whom an EBV brain persistent infection may act as a cofactor in the development of the disease. Accordingly, serum anti-EBNA-1 IgG response seems to mark MS patients compared to other inflammatory and non inflammatory conditions. Work supported by FISM (2008-R-12) and by Programma di ricerca Regione-Università 2007-2009
EBV-specific intrathecal oligoclonal antibody response in multiple sclerosis patients
CASTELLAZZI, Massimiliano;TAMBORINO, Carmine;CURRELI, Giovanna;BALDI, Eleonora;SERACENI, Silva;TOLA, Maria Rosaria;GRANIERI, Enrico Gavino Giuseppe;CONTINI, Carlo;FAINARDI, Enrico
2010
Abstract
Although Epstein-Barr virus (EBV) has recently received increasingly attention as a potential causative infectious agent in Multiple Sclerosis (MS), the significance of EBV-specific humoral immune response in MS still remains to be clarified. The aim of our study was to investigate CSF and serum levels and the presence of an intrathecal synthesis of anti-EBV IgG in MS and controls. We measured by ELISA technique cerebrospinal fluid (CSF) and serum levels of anti-EBV IgG in 100 relapsing-remitting (RR) MS patients, grouped according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity, in 109 patients with other inflammatory neurological disorders (OIND) and in 87 patients with non-inflammatory neurological disorders (NIND). Anti-EBV nuclear antigen-1 (EBNA-1) and anti viral capsid antigen (VCA) IgG levels were expressed as arbitrary units and quantitative intrathecal synthesis of anti-EBNA-1 and anti-VCA IgG was determined by Antibody Index (AI). The presence of EBV-specific CSF oligoclonal IgG bands (OCB) was assessed in MS patients by antigen-specific immunoblotting. CSF concentrations were higher in OIND than in MS (p < 0.0001) and NIND (p < 0.01) for anti-VCA IgG, and in MS than in NIND (p < 0.01) and in OIND than in NIND (p < 0.05) for anti-EBNA-1 IgG. Serum levels of anti-EBNA-1 IgG were more elevated in in MS than in OIND and NIND (p < 0.0001). Serum titers of anti-EBNA-1 IgG were inversely (p < 0.001) correlated with EDSS. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a small proportion of MS and controls (range from 1.1 to 6.4%). EBV-specific CSF-restricted OCB were detected in 25/100 (25%) MS patients. Serum levels of anti-VCA IgG were greater in MS patients without than in those with EBV-specific CSF OCB. These findings argue against a direct pathogenetic role of EBV-targeted humoral immune response in MS. However, an intrathecal release of EBV-specific oligoclonal IgG can occur in a subset of patients with MS in whom an EBV brain persistent infection may act as a cofactor in the development of the disease. Accordingly, serum anti-EBNA-1 IgG response seems to mark MS patients compared to other inflammatory and non inflammatory conditions. Work supported by FISM (2008-R-12) and by Programma di ricerca Regione-Università 2007-2009I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
