8239
Epstein Barr Virus, but Not Herpes Simplex Viruses, Is Associated with Multiple Sclerosis
Although the etiology of multiple sclerosis (MS) remains unknown, evidence suggests a role of herpesviruses (HVs), including Epstein Barr Virus (EBV) and, to a lesser extent, Herpes Simplex virus types 1 and 2 (HSV1 and HSV2). HVs have four unique routes for infection and latency within the central nervous system (CNS); olfactory nerve retrograde axonal transport, peripheral anterograde axonal transport from the trigeminal ganglia (TG), dispersion from latent reactivation, and hematogenous transport. Combined with HVs’ ability to “reactivate” after acute infection, these routes allow the virus to associate chronically with neurons, astrocytes, and oligodendrocytes which could lead to, or exacerbate, neuroinflammation frequently observed in patients with MS. However, previous studies are mixed.
Objectives:
To investigate the prevalence of HVs seropositivity in MS patients compared to non-MS neurologic control.
Methods:
A cross-sectional, single-center, cohort study. Retrospective review of clinical serologic data was obtained from MS patients and non-MS neurologic control under the clinical care of one provider (AZO) between July 2018 and December 2021. Patients with available serologic IgG data for EBV capsid antigen (EBVCA), EBNA, HSV 1, or HSV2 were included in the analysis. Frequency of positive IgG was calculated for each virus and compared between MS and non-MS controls. Chi-square or Fisher’s exact tests were conducted, as appropriate, and p-value was set at <0.05.
Results:
Serum IgG for EBVCA was tested in 209 patients (106 MS; 103 non-MS) and seropositivity confirmed in 105 (99.1%) MS patients versus 90 (87.4%) non-MS, p<0.0008. Serum EBNA IgG was tested in 100 patients (45 MS; 55 non-MS). Seropositivity was confirmed in 44 (97.8%) MS patients versus 46 (83.6%) non-MS, P=0.02 (Fisher). Serum HSV1 IgG was tested in 231 patients (116 MS; 115 non-MS). Seropositivity was confirmed in 54 (46.6%) MS patients versus 54 (47.0%) non-MS, P=0.95. Serum HSV2 IgG was tested in 233 patients (117 MS; 116 non-MS). Seropositivity was confirmed in 27 (23.1%) MS patients versus 33 (28.4%) non-MS, P=0.35.
Conclusions:
People with MS have a significantly higher prevalence of EBVCA and EBNA IgG seropositivity than non-MS neurologic control. No difference was observed in the frequency of HSV1 or HSV2 seropositivity. Our findings further support an association between EBV infection and MS, not that of HSV1 or HSV2 and MS.