This mechanistic review described how vitamin D status modulates immune responses to Epstein-Barr virus infection, proposing a synergistic risk model for MS. Low vitamin D decreases immune tolerance (shift from Th2 to Th1 responses) while simultaneously increasing susceptibility to EBV reactivation and persistent infection. Vitamin D receptors are expressed on EBV-infected B cells and antigen-presenting cells; active vitamin D suppresses antibody production, inhibits T cell proliferation, and polarizes responses toward protective Th2 phenotype. The author hypothesized that MS develops through combined effects of EBV infection and vitamin D deficiency, with each factor amplifying the other's pathogenic effects.
The synergistic risk model explains why MS is rare when either factor is absent (protective childhood EBV exposure or adequate vitamin D) but common when both risk factors coexist (late EBV infection plus vitamin D deficiency). This mechanism suggests MS prevention might target either factor: early EBV exposure establishing tolerance, or maintaining adequate vitamin D to promote immune tolerance despite EBV infection. For MS patients, this research strongly supports vitamin D supplementation as potentially disease-modifying, particularly in EBV-seropositive individuals, suggesting vitamin D supplementation might both suppress autoreactive responses and reduce EBV reactivation.
