Aspects of Epstein-Barr Virus, Together and Independently, Increase Risk of MS

Researchers determined 2 aspects of Epstein-Barr virus (EBV), levels of anti—Epstein-Barr virus nuclear antigen–1 (anti-EBNA-1) antibodies and history of infectious mononucleosis (IM), act together and independently to increase risk of multiple sclerosis (MS), according to a study published in Frontiers in Neurology.

Researchers used data from 2 population-based case-control studies in Sweden to determine the extent to which the relationship between IM history and MS risk is influenced by high levels of anti-EBNA-1 antibodies and vice versa. Human leukocyte antigen (HLA) genes, which are associated with MS, were analyzed to determine and gauge MS development. HLA class 1 genes are also involved in controlling EBV, authors said.

In total, the study included 5316 cases and 5431 matched controls. Researchers compared subjects with different HLA alleles, EBNA-1, and IM status. Odds ratios (ORs) were calculated with 95% CIs. “Trend test for a dose-response relationship regarding anti-EBNA-1 antibody levels and risk of MS was performed by using a continuous variable for anti-EBNA-1 antibody levels in a logistic regression model,” researchers said.

The study yielded the following results:

• Elevated anti-EBNA-1 antibody levels increased MS risk by 3-fold (adjusted OR, 3.1; 95% CI, 2.9-3.4)
• Risk of MS increased with increasing anti-EBNA-1 antibody levels (P for trend <.0001)
• A weak correlation exists between anti-EBNA-1 antibody levels and IM (P = .07 among controls and P = .01 among cases)
• IM history increased the risk of MS by 70% (adjusted OR, 1.7; 95%, CI 1.5-1.9)

In addition, researchers found that for subjects categorized based on EBNA-1 status and IM history, “each factor increased MS risk in the absence of the other; high anti-EBNA-1 antibody levels conferred a 3-fold increased risk of disease (adjusted OR, 3.1; 95% CI, 2.8-3.3), whereas IM history increased MS risk by 50% (adjusted OR, 1.5; 95% CI, 1.4-1.7).”

Results support the hypothesis that both aspects of EBV infection act synergistically to increase MS risk and are thus partly involved in the same biological pathways.

Reference

Hedström AK, Huang J, Michel A, et al. High Levels of Epstein—Barr virus nuclear antigen-1-specific antibodies and infectious mononucleosis act both independently and synergistically to increase multiple sclerosis risk. Front Neurol. 2020;10(1368). doi:10.3389/fneur.2019.01368.