In 2022, two studies received quite a bit of attention. One showed that EBV seroconversion occurs in the years prior to MS diagnosis in virtually every patient, and that serum levels of the neuronal damage biomarker neurofilament light (NfL) rose following EBV infection. Another paper showed anti-EBNA (Epstein-Barr nuclear antigen) antibodies in the cerebrospinal fluid cross-react with the central nervous system antigen GlialCAM in some MS patients.
Based on those studies, “it’s tempting to speculate that primary EBV infection could be a trigger to the autoimmune process suspected for MS,” said Tilman Schneider-Hohendorf, PhD, during a presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Dr. Schneider-Hohendorf, who is a postdoctoral fellow at the University of Münster, Germany, presented a new study that added more evidence that EBV may be a key player in MS pathogenesis. He and colleagues conducted a genetic analysis of patient T cells and found evidence that EBV viral activity may be occurring during MS.
A viral pathway to MS
Asked for comment, Bruce Cree, MD, PhD, said: “I think it is a very interesting one, because what we know about EBV is that it’s a risk factor for MS. So many studies performed over the last 20 years have shown a very strong association between EBV infection and the occurrence of MS. Studies have shown quite conclusively that EBV infection precedes MS in almost every patient, and that EBV infection is followed by a rise in serum NfL, which is a biomarker of neuronal damage. You have EBV infection, and then typically several years later a rise in serum concentrations of this marker of neuronal injury, and this is all in a presymptomatic state. Then that is followed by the onset of clinical symptoms in MS. That temporal sequence, I think, is very convincing,” said Dr. Cree, who is a professor of clinical neurology at the University of California, San Francisco.
He pointed out that EBV is not the sole causal pathway of MS, since genetic and environmental factors are known to be involved. “Nonetheless, it’s very strong evidence to indicate that this virus is involved in disease pathogenesis,” said Dr. Cree.
The new research takes the work a step further by revealing a population of T cells in MS patients that appear to be responding directly to EBV during active viral disease. That could be telling because most people who experience an EBV infection and experience mononucleosis recover, and some never even realize they have been infected. As a herpes virus, EBV remains in a latent state in B cells and other immune cells. “We know that you need an EBV infection (to trigger MS), but is EBV in some way continuing to be active in MS?” said Dr. Cree.
Other groups have looked for such evidence, but results have been mixed. Dr. Cree’s own group looked for evidence of EBV in spinal fluid of MS patients when they first present with symptoms, and could find no evidence. On the other hand, an autopsy study of MS patients has found evidence of chronic EBV infection in and around the brain, including the meninges, which could implicate the B cells found in that region. Another study found EBV-targeting antibodies that cross react with neuronal antigens in the cerebral spinal fluid of MS patients. “So depending on the assay used and the types of investigation, there is variable evidence to indicate that EBV has a role in ongoing MS pathogenesis – that it isn’t just a risk factor for MS that triggers the disease but potentially has a role in determining the course of MS,” said Dr. Cree.