myelin-basic-protein and Epstein-Barr-Virus-Infections

Myelin basic protein (MBP) is thought to be one of the key autoantigens in multiple sclerosis (MS) development. A recent study described the association of the single nucleotide polymorphism (SNP) rs12959006, within the

Topics: Adult; Epstein-Barr Virus Infections; Female; Follow-Up Studies; Genotype; Herpesvirus 4, Human; Herpesvirus 6, Human; Humans; Male; Multiple Sclerosis, Relapsing-Remitting; Myelin Basic Protein; Polymorphism, Single Nucleotide; Prognosis; Recurrence; Retrospective Studies; Roseolovirus Infections; Sex Factors; Spain; Young Adult

Topics: B-Lymphocytes; Canada; Environment; Epstein-Barr Virus Infections; Female; Genetic Predisposition to Disease; Geography, Medical; Herpesvirus 4, Human; HLA-DRB1 Chains; Humans; Male; Meta-Analysis as Topic; Multiple Sclerosis; Myelin Basic Protein; Myelin Sheath; Myeloid Cells; Risk Factors; T-Lymphocytes; Vitamin D Deficiency

Myelin oligodendrocyte glycoprotein (MOG) may be implicated in the immunopathogenesis of multiple sclerosis (MS) inducing demyelination in the animal model of MS. In adults reported anti-MOG antibody frequencies have been variable across a number of studies and can also be detected in controls.. To measure antibodies against MOG in paediatric patients with demyelinating disorders of the central nervous system and in controls.. Serum antibodies against MOG and myelin basic protein were measured by ELISA, flow cytometry (FACS) and in the liquid phase in 11 children with acute disseminated encephalomyelitis (ADEM), 22 children with MS, seven children with acute viral encephalitis and 13 healthy controls. The serostatus of Epstein-Barr virus (EBV) infections were assessed.. Anti-MOG antibodies, measured either by ELISA or FACS were exclusively detected in children with demyelination. In ADEM these antibodies were highly reactive. Anti-MBP reactivity was detectable equally in all groups. The presence of either autoantibodies did not associate with EBV serostatus, age, gender or disease course.. This study independently corroborates recently published results of seroprevalence and specificity of the assay. Due to their low sensitivity anti-MOG antibodies will not serve as disease-specific biomarkers, but could help to support the diagnosis of ADEM in difficult cases.

Topics: Adolescent; Autoantibodies; Biomarkers; Chi-Square Distribution; Child; Child, Preschool; Demyelinating Diseases; Diagnosis, Differential; Encephalitis, Viral; Encephalomyelitis, Acute Disseminated; Enzyme-Linked Immunosorbent Assay; Epstein-Barr Virus Infections; Female; Flow Cytometry; France; Germany; Humans; Immunity, Humoral; Male; Myelin Basic Protein; Myelin Proteins; Myelin-Associated Glycoprotein; Myelin-Oligodendrocyte Glycoprotein; Nerve Tissue Proteins; Predictive Value of Tests; Retrospective Studies; Transcription Factors

Symptomatic primary Epstein-Barr virus (EBV) infection and elevated humoral immune responses to EBV are associated with an increased risk of developing multiple sclerosis (MS). We explored mechanisms leading to this change in EBV-specific immunity in untreated patients with MS and healthy virus carriers matched for MS-associated HLA alleles. MS patients showed selective increase of T cell responses to the EBV nuclear antigen 1 (EBNA1), the most consistently recognized EBV-derived CD4(+) T cell antigen in healthy virus carriers, but not to other EBV-encoded proteins. In contrast, influenza and human cytomegalovirus-specific immune control was unchanged in MS. The enhanced response to EBNA1 was mediated by an expanded reservoir of EBNA1-specific central memory CD4(+) T helper 1 (Th1) precursors and Th1 (but not Th17) polarized effector memory cells. In addition, EBNA1-specific T cells recognized myelin antigens more frequently than other autoantigens that are not associated with MS. Myelin cross-reactive T cells produced IFN-gamma, but differed from EBNA1-monospecific cells in their capability to produce interleukin-2, indicative of a polyfunctional phenotype as found in controlled chronic viral infections. Our data support the concept that clonally expanded EBNA1-specific CD4(+) T cells potentially contribute to the development of MS by cross-recognition of myelin antigens.

Topics: Adult; Aged; Antibodies, Viral; Autoantigens; Case-Control Studies; CD4-Positive T-Lymphocytes; Cross Reactions; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; Female; Herpesvirus 4, Human; Humans; Immunoglobulin G; Interferon-gamma; Interleukin-2; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; T-Lymphocyte Subsets

The mechanisms leading to CNS disorders after EBV infections are unclear. We report the case of a patient who developed a severe, but reversible, encephalopathy following an infectious mononucleosis. We detected no EBV DNA in the blood or in the cerebrospinal fluid (CSF) and no EBV-specific antibodies in the CSF. However, we found a potent MOG-specific cellular and humoral immune response. Interestingly, MOG-specific cellular immune response rapidly decreased, paralleling the improvement of clinical condition. In conclusion, this detailed study shows that acute EBV infection can trigger a potent auto-inflammatory response in the CNS, without evidence of an overt infection.

Topics: Adult; Antibodies; Brain Diseases; Cell Proliferation; Disease Progression; Enzyme-Linked Immunosorbent Assay; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Interferon-gamma; Male; Myelin Basic Protein; Myelin Proteins; Myelin-Associated Glycoprotein; Myelin-Oligodendrocyte Glycoprotein

Epstein-Barr virus-specific CD4+ T cells could be involved in the pathogenesis of multiple sclerosis, provided they can gain entry to the intrathecal compartment. The authors have previously demonstrated that cerebrospinal fluid T cells from multiple sclerosis patients recognize autologous Epstein-Barr virus-transformed B cells. They now report that CD4+ T cells specific for the Epstein-Barr virus DNA polymerase peptide EBV 627-641 were present in the cerebrospinal fluid from one of two multiple sclerosis patients, and that a high proportion of these CD4+ T cells cross-recognized an immunodominant myelin basic protein peptide, MBP 85-99. In the observed patient, the proportion of EBV 627-641-specific CD4+ T cells seemed to exceed 1/10,000 in cerebrospinal fluid, compared to approximately 1/100,000 in blood. These findings prove that Epstein-Barr-virus specific CD4+ T cells can gain access to the intrathecal compartment, and suggest that Epstein-Barr virus-specific CD4+ T cells could target myelin basic protein in the central nervous system.

Topics: Adult; CD4-Positive T-Lymphocytes; Cerebrospinal Fluid; Cross Reactions; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein