EBV Infections Evident in All 901 MS Patients in German Study

Supporting evidence that infection with Epstein-Barr virus (EBV) could be one of the root causes of multiple sclerosis (MS), a recent study found all of its 901 early disease patients carry antibodies against this virus, meaning that all are or have been exposed to it.

The study, “Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis,” was published in the Journal of Neurology, Neurosurgery, and Psychiatry.

EBV infections have been proposed to be a root cause of MS, with researchers believing that the virus is able to mislead the immune system into developing antibodies against the protective myelin sheath of nerve cells.

But for this hypothesis to be true, everyone with MS had to be infected with the virus at some point in their lives.

Despite the high prevalence of patients carrying antibodies against EBV (98%–100%), some studies have shown that it is possible to have MS without this viral infection.

But researchers have wondered whether this is because patients were misdiagnosed with MS, or because tests used to measure EBV antibodies were not accurate enough to detect all positive cases.

To find the real prevalence of EBV infections in large group of MS patients, researchers at the German Competence Network Multiple Sclerosis examined 901 people with early MS included in the German National MS cohort, and tested them for EBV antibodies.

These people, ages 27 to 41 years, had either clinically isolated syndrome (42.2%) — defined as first evident symptoms of inflammatory demyelination — or early relapsing-remitting MS (57.8%).

As controls, the team used data from 16,163 individuals tested for EBV for routine diagnostic purposes.

Patients were specifically tested for antibodies against the EBNA-1 protein, which is a marker of past EBV infection, and the VCA protein, which marks ongoing and past infections. Those with negative blood serum results were then tested for the same antibodies using another method.

Results showed 839 of these MS patients (93.1%) were positive for EBNA-1 antibodies, and 45 of the 62 people without these antibodies were positive for VCA antibodies.

The remaining 17 patients tested positive for these EBV antibodies when another method (immunoblot) was used.

All MS patients analyzed were or had been infected with EBV.

“The key result of this study is a complete EBV seropositivity in a large cohort (n=901) of patients with early MS,” the researchers wrote. “While this finding is consistent with the known high EBV seroprevalence in MS, the absence of any EBV-seronegative patients with early MS in our cohort appears remarkable and further strengthens the evidence for an association of EBV infection and MS.”

But, they added, EBV infection is likely not the disease’s sole cause.

Individuals serving as controls also had a high prevalence of EBV infections across distinct age groups, with the proportion of people with antibodies increasing with age.

Among those in the 20 to 40 years old range — notable because it is the typical age for MS clinical onset — the prevalence of EBV infections for patients was 100% and 95.2% among controls.

“The higher EBV seropositivity rate in patients with early MS (100%) as compared with persons in the hospital population (95.2%) in the age range of 20–40 years is consistent with previous data, and appears compatible with the concept that EBV may be a necessary but not sufficient factor for the development of MS,” researchers wrote.

Still, the fact that all MS patients analyzed were or had been exposed to EBV, including those with the earliest manifestations of MS, strengthens “the concept that EBV infection precedes the clinical onset of MS and suggests that EBV exerts its role early in the development of MS,” the team added.

Researchers also suggested that “a negative EBV [antibody result] in patients with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS.”