Epstein-Barr Virus and Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a neurologic disease affecting myelinated nerves in the central nervous system (CNS). The disease often debuts as a clinically isolated syndrome, e.g., optic neuritis (ON), which later develops into relapsing-remitting (RR) MS, with temporal attacks or primary progressive (PP) MS. Characteristic features of MS are inflammatory foci in the CNS and intrathecal synthesis of immunoglobulins (Igs), measured as an IgG index, oligoclonal bands (OCBs), or specific antibody indexes. Major predisposing factors for MS are certain tissue types (e.g., HLA DRB1*15:01), vitamin D deficiency, smoking, obesity, and infection with Epstein-Barr virus (EBV). Many of the clinical signs of MS described above can be explained by chronic/recurrent EBV infection and current models of EBV involvement suggest that RRMS may be caused by repeated entry of EBV-transformed B cells to the CNS in connection with attacks, while PPMS may be caused by more chronic activity of EBV-transformed B cells in the CNS. In line with the model of EBV’s role in MS, new treatments based on monoclonal antibodies (MAbs) targeting B cells have shown good efficacy in clinical trials both for RRMS and PPMS, while MAbs inhibiting B cell mobilization and entry to the CNS have shown efficacy in RRMS. Thus, these agents, which are now first line therapy in many patients, may be hypothesized to function by counteracting a chronic EBV infection.

Pathogenesis of autoimmune demyelination: from multiple sclerosis to neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody‐associated disease

“…Arguably, most renowned is the association between MS and Epstein–Barr virus (EBV) with almost all MS patients having been previously infected with EBV 76 . EBV Ab seropositivity is observed at higher rates in MS patients and is strongly correlated with disease onset 77,78 . Additionally, EBV‐induced infectious mononucleosis is found to be associated with a twofold risk of developing MS 77 .…”

“…EBV Ab seropositivity is observed at higher rates in MS patients and is strongly correlated with disease onset 77,78 . Additionally, EBV‐induced infectious mononucleosis is found to be associated with a twofold risk of developing MS 77 . Autoreactive B cells latently infected with EBV are proposed to contribute to MS pathogenesis by evading elimination of CD8 + T cells and accumulating within the CNS, producing myelin‐reactive antibodies and survival signals for T cells 78 .…”

Infections and Multiple Sclerosis: From the World to Sardinia, From Sardinia to the World

“…EBV is related to several diseases that develop years after the primary infection. It has been hypothesised that a decreased capacity to control EBV by the immune system could promote the onset of late EBV-related diseases, such as cancer, MS, and other autoimmune disorders (22). A defective T cell control of EBV in patients with MS has been reported (23).…”

“…Nevertheless, the presence of EBV in the brain could be not a peculiar characteristic of MS. Moreover, many viruses persisting in a latent stage are neurotrophic and could be found inside the brain (22). Recently, antibodies against specific epitopes in EBNA-1 crossreacting with MBP have been recognised in the sera of patients with MS and not of healthy controls (29).…”

Stress-Induced Epstein-Barr Virus Reactivation

“…This illness is most commonly seen in adolescents and young adults and presents with fatigue, fever, pharyngitis, cervical lymphadenopathy, and lymphocytosis [ 5 , 6 ]. EBV has been associated with other diseases including chronic fatigue syndrome, Epstein-Barr virus-related post-transplant lymphoproliferative disease, multiple sclerosis, encephalitis, cerebellar ataxia, Alzheimer’s disease, oral hairy leukoplakia, and autoimmune conditions such as Grave’s Disease, Sjögren’s syndrome, and rheumatoid arthritis [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Notably, there is a well-established connection between EBV and malignancies including Hodgkin’s lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma, primary central nervous system lymphoma, T cell lymphoma, certain gastric carcinomas, and nasopharyngeal carcinoma (NPC) [ 15 , 16 , 17 , 18 ].…”