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Infectious causes of multiple sclerosis
1Department of Neurology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. don.gilden@uchsc.edu <don.gilden@uchsc.edu>
Abstract:
Multiple sclerosis (MS) is a serious chronic neurological disorder in which demyelination and inflammation occur in the white matter of the CNS. The findings of many epidemiological studies and a discordance of MS in monozygotic twins suggest that the disorder is acquired. The most likely cause is a virus because more than 90% of patients with MS have high concentrations of IgG, manifest as oligoclonal bands, in the brain and CSF. Most chronic inflammatory CNS disorders are infectious. More indirect evidence that MS is caused by a virus is the association of several viruses with demyelinating encephalomyelitis in human beings, and the induction of demyelination in animals infected with viruses in research. Nevertheless, no virus has been isolated from the brains of patients who had MS. Molecular analysis of IgG gene specificity in the brain and CSF of those with MS has shown features of an antigen-driven response: clonal amplification and extensive somatic mutations. A viral antigen against which the IgG in MS brain and CSF is directed might be identified.
Insights
Multiple sclerosis (MS) is an acquired neurological disorder likely caused by a virus. Research shows specific immune responses in the brain and cerebrospinal fluid (CSF) of MS patients, suggesting a viral antigen target.
Area of Science:
- Neuroimmunology
- Virology
- Genetics
Background:
- Multiple sclerosis (MS) is a chronic central nervous system (CNS) demyelinating and inflammatory disorder.
- Epidemiological studies and twin discordance suggest MS is acquired, with viral infection being a leading hypothesis.
- Elevated IgG with oligoclonal bands in the CNS of MS patients indicates an antigen-driven immune response.
Purpose of the Study:
- To explore the potential viral etiology of multiple sclerosis.
- To investigate the immune response in the CNS of MS patients for evidence of viral antigen specificity.
Main Methods:
- Analysis of IgG gene specificity in brain and cerebrospinal fluid (CSF) from MS patients.
- Examination of molecular features indicative of an antigen-driven immune response, such as clonal amplification and somatic mutations.
Main Results:
- Molecular analysis revealed features of an antigen-driven immune response in the IgG from MS patients' CNS.
- Evidence of clonal amplification and extensive somatic mutations in IgG genes suggests a specific target.
Conclusions:
- The immune response in multiple sclerosis brain and CSF exhibits characteristics of a specific, antigen-driven process.
- Identifying the specific viral antigen targeted by the IgG in MS patients is a crucial next step.
