First, the lack of spinal cord MRI examinations suggests the possibility that some active lesions could be missed in our series, leading to a potentially inappropriate allocation of patients to the MRI inactive group

First, the lack of spinal cord MRI examinations suggests the possibility that some active lesions could be missed in our series, leading to a potentially inappropriate allocation of patients to the MRI inactive group. EBV-specific IgG OCB had low affinity in all 24 RRMS patients analyzed. Conclusions Our findings do not support the potential role of an EBV persistent brain chronic infection in MS and suggest that an EBV-specific intrathecal oligoclonal IgG production can occur in a subset of MS patients as part of humoral polyreactivity driven by chronic brain inflammation. Background Multiple Sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) of supposed autoimmune origin, which is currently believed to be mediated by a combined attack directed by both T and B cells [1]. Although disease etiology remains largely unknown, epidemiological observations suggest the potential implication of an infectious organism as a causative agent of MS [2]. In this setting, an ideal candidate is represented by Epstein-Barr virus (EBV), a human -herpesvirus with a widespread distribution in the human population, which can infect and activate B-lymphocytes and persists latently for life [3]. Seroepidemiological studies have shown that there could be a strong association between MS and EBV. A past infectious mononucleosis (IM) was found to be more frequent, and the seroprevalence of anti-Epstein Barr nuclear antigen 1 (EBNA-1) and anti-viral capsid antigen (VCA) IgG was higher in MS patients than in controls [4C6]. High serum levels of anti-EBNA-1 IgG increased the risk of developing MS [7], correlated with disease activity Abemaciclib Metabolites M2 [8] and predicted the conversion from clinical isolated syndrome (CIS) to definite MS [9]. Elevated serum concentrations of anti-VCA IgG were related to gray matter atrophy [10]. The role of EBV in Abemaciclib Metabolites M2 MS pathogenesis was in part supported by the experimental demonstration that EBV proteins and myelin-basic protein epitopes share structural similarity [11]. However, conflicting results have been obtained in cellular, molecular and neuropathological studies since, in MS patients, blood EBV-specific CD8+ T cell response was found increased, Rabbit polyclonal to SP3 decreased or absent; cerebrospinal Abemaciclib Metabolites M2 fluid (CSF) and blood EBV DNA load was high or not measurable; and the detection of EBV-infected B cells in brain lesions was inconsistent [3,5,7,12]. Controversial findings were also reported in quantitative and qualitative analysis of intrathecal synthesis of anti-EBV IgG in MS. An antibody index (AI) suggestive of intrathecally produced anti-EBV IgG was more represented [13] or equivalent [14C19] in MS patients compared to controls, whereas the detection of CSF-restricted EBV-specific IgG oligoclonal bands (OCB) in MS patients was highly variable, ranging from 0% to 44% [16,20C24]. Nevertheless, none of the previous studies investigated the affinity distributions of intrathecally released anti-EBV antibodies. Therefore, the actual relevance of EBV in MS still remains to be elucidated. In this regard, it is particularly crucial to determine the exact nature of EBV-specific intrathecal humoral immune response since the key feature of chronic CNS infections is the presence of targeted intrathecaly produced high-affinity oligoclonal antibodies, of which only 20% are specific to the causative agent [2]. To address the question of whether an EBV persistent brain infection exists in MS, in this study we sought to verify the frequency of EBV-specific oligoclonal IgG restricted to CSF and their affinity distributions in a large number of MS patients and controls. Methods Study design This study included 100 consecutive patients with relapsing-remitting definite MS (RRMS) according to the currently accepted criteria [25] (Table?1) followed by the MS Center of Ferrara (Italy) during the period from June 2004 to December 2008. MS relapse was defined as the onset of new or recurrent.