Risk of multiple sclerosis (MS) increased 32-fold after infection with Epstein-Barr virus (EBV) but was unchanged after other viral infections, a longitudinal analysis showed.
Data from more than 10 million U.S. military recruits monitored over a 20-year period — 955 of whom were diagnosed with incident MS during their service — showed that MS had a hazard ratio of 32.4 (95% CI 4.3-245.3, P<0. 001) with EBV seroconversion compared with persistent EBV seronegativity, reported Alberto Ascherio, MD, DrPH, of the Harvard T.H. Chan School of Public Health, and co-authors in Science.
The researchers pointed out that MS is a result of EBV infection. Ascherio stated in a statement that while the hypothesis that EBV causes MS is well-supported by other research groups for many years, this study provides compelling evidence of causality.
” This is a significant step as it suggests that most MS cases can be prevented by stopping EBV infections. Targeting EBV could also lead to the discovery and treatment of MS.” he said.
Multiple strands of data indicate that EBV infection and MS are causal, stated Gavin Giovannoni MBBCh, PhD. He was an academic neurologist at Queen Mary University of London, England.
“Now Alberto Ascherio and colleagues show in a large cohort study of young adults in the U.S. military that the risk of multiple sclerosis increased 32-fold after infection with EBV, which was unchanged after infection with other viruses, including cytomegalovirus, a closely related herpesvirus with similar patterns of transmission,” Giovannoni told MedPage Today.
“A new and exciting finding was that blood neurofilament light chains, which are markers of neurodegeneration, increased in subjects after EBV infection. This indicates presymptomatic MS disease onset.” he said. These findings reinforce the causal link between EBV infection and MS, and support ongoing trials targeting EBV as a therapeutic strategy to treat MS. These findings also support ongoing clinical trials that target EBV to treat MS .”
Prior research has found increased serum antibodies to EBV in 99.5% of MS patients and 94% of healthy individuals, observed William Robinson, MD, PhD, and Lawrence Steinman, MD, both of Stanford University, in an accompanying editorial.
” Nearly everyone has EBV. However, only a few people develop MS,” Robinson & Steinman wrote. “In MS pathogenesis, there are other factors such as genetic susceptibility. “
The editorialists noted that the mechanisms linking EBV to MS are still elusive. EBV-related B cell transformation is possible, and molecular mimicry is also possible. They wrote that EBV could also mediate the bystander injury to the axon or its surrounding sheath, as well as defective clearance of infected cells. “CD8+T cells that are specific for EBV-lytic proteins are found in MS brain lesions. A persistent EBV infection [central nervous system] could stimulate CD8+ T Cell responses that mediate CNS injuries. “
Ascherio and his colleagues analysed serum samples collected by the Department of Defense every two years. They determined EBV status at time of first sample, and examined the relationship between EBV infection during active duty and MS onset.
Samples were drawn from a diverse U.S. military population, from 1993 up to 2013.. Most participants were under 20 at the time of their first blood collection. At baseline, no participant had MS. MS symptoms began for the median of five years after the first EBV-positive test.
Each MS case was matched to two controls, each without MS, of the same age and sex. In total, 801 MS cases and 1,566 controls had samples available to assess EBV status over time.
EBV seropositivity was nearly ubiquitous at the time MS developed; only one of 801 MS cases was EBV seronegative at the time of MS onset