While the cause of multiple sclerosis (MS) was unknown, evidence showed that herpesviruses (HVs), such as Epstein-Barr virus (EBV) and, to a lesser extent, herpes simplex virus types 1 and 2 (HSV1 and HSV2), might play a role. The olfactory nerve retrograde axonal transport, peripheral anterograde axonal transport from the trigeminal ganglia, dispersion from latent reactivation, and hematogenous transport were the 4 distinct routes for herpesvirus infection and latency in the central nervous system. When combined with HVs’ propensity to “reactivate” after acute infection, these pathways allowed the virus to form long-term associations with neurons, astrocytes, and oligodendrocytes, potentially leading to or exacerbating neuroinflammation seen in MS patients. Previous research, on the other hand, has yielded mixed results. Therefore, for a study, researchers sought to evaluate the prevalence of HV seropositivity in MS patients with neurologic controls who did not have MS. This was a single-center, cross-sectional cohort research. Between July 2018 and December 2021, clinical serologic data from patients with MS and neurologic controls without MS under the clinical care of a single physician (A.Z.O.) were reviewed retrospectively. The study included patients with available serologic immunoglobulin G (IgG) data for EBV capsid antigen (EBVCA), EBNA, HSV1, or HSV2. The frequency of positive IgG was computed and compared between MS patients and controls for each virus. X2 or Fisher exact tests were used, as needed, with a significance level of P<.05.
Serum IgG for EBVCA was tested in 209 patients (106 MS, 103 non-MS), with seropositivity verified in 105 MS patients (99.1%) vs. 90 non-MS patients (87.4%) (P<.0008). A total of 100 patients had their serum EBNA IgG analyzed (45 MS, 55 non-MS). Seropositivity was confirmed in 44 MS patients (97.8%) vs 46 non-MS patients (83.6%) (P=.02) (Fisher). In 231 patients, serum HSV1 IgG was examined (116 MS, 115 non-MS). Seropositivity was confirmed in 54 MS patients (46.6%) compared to 54 non-MS patients (47.0%) (P=.95). In 233 patients, serum HSV2 IgG was examined (117 MS, 116 non-MS). Seropositivity was confirmed in 27 MS patients (23.1%) vs 33 non-MS patients (28.4%) (P=.35). Seropositivity to EBVCA and EBNA IgG was considerably higher in MS patients than in neurologic control persons without MS. There was no difference in the frequency of HSV1 and HSV2 seropositivity. The outcomes showed that EBV infection was linked to MS but not to HSV1 or HSV2.
