Table 1.
Evidence for Epstein-Barr virus (EBV) involvement in multiple sclerosis (MS).
| MS trait/characteristic | EBV relation | References |
|---|---|---|
| Elevated IgG index | CNS entry of EBV-infected B cells and differentiation to plasma cells | (6) |
| OCBs in CSF | CNS entry of EBV-infected B cells and differentiation to plasma cells | (6, 8) |
| Elevated FLCs | CNS entry of EBV-infected B cells and differentiation to plasma cells | (9, 10) |
| Elevated specific AIs | CNS entry of EBV-infected B cells and differentiation to plasma cells | (11–19) |
| CNS inflammatory foci | T cell attack on CNS EBV-infected B cells | (1, 2, 5) |
| Demyelination in CNS | Inflammatory damage to oligodendrocytes and stimulation of macrophages and microglia cells | (1–3) |
| AuAbs to myelin AuAgs | Inflammation-induced stimulation of (EBV-infected) B cells and damage to oligodendrocytes | (113–116) |
| Therapy with CD20 MAbs | Killing of EBV-infected B cells, prevention of CNS entry | (27, 28) |
| Therapy with integrin MAbs | Prevention of CNS entry of EBV-infected B cells | (117, 118) |
| Therapy with EBV-specific T cells | Killing of EBV-infected B cells, prevention of CNS entry | (119, 120) |
| Female preponderance | Reduced EBV control (immune suppression due to menstruation (blood loss, healing, hormonal factors) | (1–3, 30) |
| Incidence increases after puberty | Increased exposure to EBV, reduced capacity for EBV control due to thymus involution | (3) |
| HLA DRB1 predisposes | Increased entry and/or decreased immune control of EBV | (1–3, 29–40) |
| IM predisposes | Increased load of EBV-transformed B cells | (30, 54–56, 121–123) |
| VitD deficiency predisposes | Reduced EBV control (immune suppression due to vitD deficiency of leukocytes, (e.g., T cells, NK cells) | (39, 41–43) |
| Smoking predisposes | Reduced EBV control (immune suppression by smoke) and/or increased frequency of EBV reactivation | (30, 44–46) |
| Obesity predisposes | Reduced EBV control due to immune suppression | (50–53) |
Ab, Antibody; Ag, antigen; AI, antibody index; AuAb, autoantibody; AuAg, autoantigen; CD, cluster of differentiation; CNS, central nervous system; EBV, Epstein-Barr virus; FLC, free light chains; HLA, human leukocyte antigen; IM, infectious mononucleosis; MAb, monoclonal antibody; NK, natural killer; VitD, vitamin D.