Smoking, low exposure to ultraviolet (UV) radiation, low serum vitamin D levels and past infection with Epstein-Barr virus (EBV) all are well-established risk factors for developing multiple sclerosis (MS). Considerable evidence also suggests that infection with HHV-6A might be one trigger of MS.
In 2019, investigators from Karolinska Institute reported that elevated antibodies to HHV-6A IE-1A predict an increased risk of developing MS (Engdahl 2019). The same group, led by Anna Karin Hedstrom, Head of Clinical Neuroscience at Karolinska Institute, sought to elucidate potential interactions between HHV-6A and the other environmental/lifestyle risk factors for MS.
Two Swedish population-based case-control studies including 5993 cases and 5995 controls were used. Logistic regression models were then used to determine the independent risk for developing MS linked to increased HHV-6A IE1-A antibody levels, after adjusting for other MS risk factors. The group used a Luminex based assay developed in collaboration with Tim Waterboer at the German Cancer Center. It is currently the only serological assay that can differentiate between HHV-6A and HHV-6B antibodies.
Those with high HHV-6A antibody levels were found to have a 1.5-fold increased risk of developing MS (Odds ratio = 1.5, 95% CI = 1.4-1.6), confirming previous findings. In people with both high levels of antibodies to HHV-6A IE-1A and other risk factors the risk of developing MS was increased: with smoking OR=2.2 (95% CI = 2.0-2.4); with low UV exposure OR = 2.2 (95% CI = 1.8-2.6); with low vitamin D levels OR = 2.2 (95% CI = 1.6-3.0).
The authors conclude that high HHV-6 IE1-A antibody levels act synergistically with these other risk factors and discuss some of the mechanisms by which these risk factors might become synergistic.
Read the full article: Wu 2021