How does EBV cause MS? #MSBlog #MSResearch
"This study confirms several previous studies and demonstrates that the majority of MSers do not have synthesis of EBV specific antibodies in the spinal fluid. This is an important finding and indicates that direct EBV infection of the brain spinal cord is unlikely to be the cause of MS. Why do I say this? In infections of the CNS (central nervous system) with known viruses, for example measles, mumps, rubella and herpes, almost all the immunoglobulin (antibody) bands react against components of the infecting virus and they tend to do so with high affinity; high affinity simply means the antibodies bind the relevant virus very strongly. The high affinity indicates that the virus is responsible for driving the immune response. If we discover a viral cause of MS the oligoclonal bands will almost certainly bind with high affinity to the causative virus. This raises the question how EBV is involved in the causal pathway of MS? I wish I knew. I suspect the EBV is interacting with another virus to cause MS. We call this this dual viral hypothesis. For example, EBV may be transactivating an endogenous retrovirus and it is the latter virus that is important. Despite this finding I still think we need to test antiviral drugs that target EBV in MS."
"Ideas on how EBV causes MS are welcome!"
Epub: Castellazzi et al. Epstein-Barr virus-specific intrathecal oligoclonal IgG production in relapsing-remitting multiple sclerosis is limited to a subset of patients and is composed of low-affinity antibodies. J Neuroinflammation. 2014;11(1):188.
Background: The purpose of this study was to investigate intrathecal production and affinity distributions of Epstein-Barr virus (EBV)-specific antibodies in MS and controls.
Methods: Cerebrospinal fluid (CSF) and serum concentrations, quantitative intrathecal synthesis, oligoclonal bands (OCB) patterns and affinity distributions of anti-Epstein Barr virus (EBV) antibodies were evaluated in 100 relapsing-remitting MS (RRMS) patients and 200 age- and sex-matched controls with other inflammatory neurological disorders (OIND) and other non-inflammatory neurological disorders (NIND).
Results: Levels of anti-EBNA-1 and anti-viral capsid antigen (VCA) IgG were different in both the CSF (P <0.0001 and P <0.01, respectively) and serum (P <0.001 and P <0.05, respectively) among the RRMS, OIND and NIND. An intrathecal synthesis of anti-EBNA-1 IgG and anti-VCA IgG, as indicated by the antibody index, was underrepresented in the RRMS, OIND and NIND (range 1 to 7%). EBV-specific OCB were detected in 24% of the RRMS patients and absent in the controls. High-affinity antibodies were more elevated in the RRMS and in the OIND than in the NIND for CSF anti-EBNA-1 IgG (P <0.0001) and anti-VCA IgG (P <0.0001). After treatment with increasing concentrations of sodium thiocyanate, the 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.