Findings suggest that viral reactivation may trigger or sustain autoimmune responses in MS.
Relapsing-remitting multiple sclerosis (RRMS) is the most common form of MS, characterized by immune-mediated attacks on myelin in the central nervous system. While previous evidence links viral reactivation (notably Epstein-Barr virus [EBV] and human herpesvirus 6 [HHV-6]) to MS, the relationship between viral markers and autoimmune responses to myelin proteins has been unclear.
An international group of investigators studied 55 RRMS patients and 63 healthy controls matched for age, gender and BMI. The study aimed to assess IgG, IgA, and IgM antibody responses to seven myelin-related proteins in RRMS patients versus healthy controls, determine the diagnostic and prognostic value of these immune responses and investigate associations between these autoimmune responses and markers of EBV and HHV-6 reactivation.
The assessments included:
- Antibody (IgG, IgA, IgM) levels against MBP, PLP, MOG-35-55, MOG-31-55, CIT-MOG, MAG-37-60, GLIAL-CAM-370-399 measured by ELISA.
- Antibody responses to EBV nuclear antigen 1 (EBNA-1) and dUTPases of EBV and HHV-6.
- Clinical disability and disease progression assessed using EDSS and MSSS scores.
Fasting blood samples were obtained at the same time of day and treated utilizing a standardized protocol.
RRMS patients had significantly higher IgG, IgA, and IgM responses to all seven myelin-related proteins compared to controls (all p < 0.001).
Combining IgG-MBP and IgM-MAG-37-60 provided 96.6% accuracy (sensitivity 95.7%, specificity 95.2%) in distinguishing RRMS from controls.
EBV and HHV-6 reactivation drive autoimmune responses targeting myelin proteins in RRMS.
This study identified the most influential myelin associated biomarkers associated with RRMS and its severity. The investigators pooled the effects of EBNA, dUTPases-EBV, and dUTPases-HHV-6 as explanatory variables against all myelin-associated markers and found that viral antigens could predict 47.4% of the variance in the IgG/M/A responses to all myelin associated markers. Additionally, 77.9% of the variance in IgA-GLIAL-CAM was predicted by EBNA and dUTPases-HHV-6. The results support the role of viral reactivation in MS, and potentially in other autoimmune mediated disease.
Read the full text: Vojdani 2025