Study pools data from nearly 30,000 people with MS.
Investigators from multiple institutions in Iran performed a meta-analysis of case-control and cross-sectional studies reported over the past 30 years to look for associations of herpesviruses with MS. The analysis involved 134 studies including nearly 30,000 people with MS, from multiple continents. The multiple studies used different diagnostic techniques (ELISA, IF, PCR) and assessed different types of specimens—serum, PBMCs, spinal fluid, urine, saliva and biopsy tissue.
The odds ratios linking three human herpesviruses to MS were statistically significant: EBV OR 3.33 (95% CI 2.54-4.35); HHV-6 OR 2.81 (95% CI 2.29-3.47); VZV OR 1.83 (95%CI 1.07-3.13). A non-significant negative association was seen for CMV.
Neurotropic herpesviruses long have been suspected as triggering some cases of multiple sclerosis (MS). In the past 20 years, most of the research has focused on Epstein-Barr virus (EBV). In a prospective study among nearly 10,000 new entrants into the U.S. military, a very strong association was found between new primary EBV infection and the subsequent development of MS over the next several years (Bjornevik 2022). At the same time, the study failed to find a similar association with HSV-1, HSV-2, CMV, VZV or HHV-6B. However, curiously, the study did not assess HHV-6A, which has been linked to MS in multiple studies (Leibovitch 2018; Komaroff 2020; Piotrowski 2023).
The possibility that EBV infection might trigger an autoimmune attack on myelin through molecular mimicry gained credence with the discovery that EBV nuclear antigen 1 (EBNA1) is very similar to GlialCAM, a molecule that is prominent in astrocytes and oligodendrocytes (myelin-generating cells) and that is expressed heavily in MS plaques (Lanz 2022).
This meta-analysis adds to the evidence that HHV-6 (primarily HHV-6A) and possibly VZV, along with EBV, should be considered possible triggers of some cases of MS.
Read the full article: Khalesi 2023