Is MS an auto-immune disease or a chronic gammaherpesvirus infection?

Area of Science:

• Neuroimmunology
• Epidemiology
• Virology

Background:

• Multiple sclerosis (MS) exhibits geographical variations, including latitude gradients and distinct clusters.
• Previous research has explored genetic, autoimmune, and environmental factors in MS etiology, with varying degrees of conclusive evidence.

Purpose of the Study:

• To critically review 75 years of geographical-epidemiological findings in MS.
• To analyze the roles of genetics, autoimmune theories, and environmental factors, including specific infectious agents, in MS pathogenesis.

Main Methods:

• Comprehensive review and analysis of existing epidemiological data on MS distribution and migration patterns.
• Scrutiny of evidence from genetic and twin studies concerning MS etiology.
• Evaluation of environmental factors and candidate infectious agents, including Marek's disease virus (MDV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6).

Main Results:

• Geographical patterns and environmental factors in MS clusters (e.g., Faroes, Key West) suggest potential common environmental causes.
• Evidence for genetics and general autoimmune theories as primary causative factors in MS pathogenesis is considered limited.
• Positive laboratory findings link Marek's disease virus (MDV) and Epstein-Barr virus (EBV) antigen in MS patients, and Human Herpesvirus 6 (HHV-6) was found in MS brain oligodendrocytes but not in controls.

Conclusions:

• Genetics play a role in individual immune resistance to infectious agents, particularly herpesviruses.
• Genetics are less critical to the pathogenesis of multiple sclerosis (MS) itself.
• Specific herpesviruses, including HHV-6, EBV, and MDV, are implicated as significant factors in MS pathogenesis.