April 8, 2003
By Paula Moyer
Children who have multiple sclerosis (MS) are more likely than healthy children to be seropositive for Epstein-Barr virus (EBV), according to researchers.
"EBV seropositive status is significantly associated with paediatric MS," said Brenda L. Banwell, MD, the director of the paediatric MS unit at the Hospital for Sick Children in Toronto, Ontario, Canada. Because of EBV's lifelong effects on B cell proliferation and T cell surveillance, it "may play a pivotal role in the autoimmune milieu that fosters MS." She presented findings of her team's study here at the 55th Annual Meeting of the American Academy of Neurology.
Dr. Banwell and her colleagues wanted to compare the seropositive status for common viruses in patients with paediatric multiple sclerosis and in controls. Their rationale was that several investigators have postulated that infection by a common virus such as EBV in a genetically pre-disposed host may be a pathobiological mechanism for MS.
The literature has also shown that adults with MS have higher seropositivity for EBV than controls do and that EBV infection has been associated with other demyelinating disorders, including optic neuritis and central nervous system demyelination. Further, research has shown that infection with acute mononucleosis in adulthood increases the risk of MS several times over.
One complication to testing the theory in adults is that EBV seropositivity is nearly universal by adulthood, with 90% of adults having EBV antibodies. Therefore, comparative analysis is limited between adult MS patients and controls. It was necessary to study paediatric patients, instead, she said, since fewer children are EBV-positive than are adults. Dr. Banwell and her colleagues theorised that MS patients might be EBV-positive before their healthy peers have had exposure to the virus.
The investigative team obtained serum samples from 25 children with clinically diagnosed MS and 75 age-matched controls, who were matched at a 3:1 ratio for birth year for each MS patient. Control samples were obtained from previously healthy children for whom serology had been drawn previously due to acute symptoms of abdominal pain, pharyngitis, or rash.
All 100 samples were analysed for EBV capsid antigen (EBV-VCA), EBV nuclear antigen (EBV-EBNA), and EBV early antigen (EBV-EA). The researchers also analysed all 25 MS samples and a random sampling of 15 of the age-matched control samples for parvovirus B19 (parvo B19), cytomegalovirus (CMV), and varicella zoster (VZV). The investigators coded and analysed all samples in a uniform manner by the ELISA technique (as per manufacturer s instructions). The study virologist then interpreted results in a blinded manner.
Dr. Bandwell and her co-investigators found that EBV seropositivity differed markedly between paediatric MS patients and age-matched controls. Although 89% of paediatric MS patients were positive for EBV-VCA and EBV-EBNA, which indicated a temporally remote infection, 31% of controls had such infections (p 0.0004). Among the MS patients, 3 (12%) were negative for all three EBV antigens.
The investigators found no statistical significance regarding seropositivity for the other viruses between MS patients and controls. For parvovirus B19 the infection rates were 49% and 64%, respectively (p=NS). For CMV the rates were 42% and 64%, respectively (p=NS). For VZV those rates were 88% and 92%, respectively (p=NS).
This discrepancy in EBV seropositivity between paediatric MS patients and controls is "considerably more robust" than similar studies of EBV in adult MS patients, Dr. Banwell said. The finding demonstrates the advantage of comparative studies in which healthy subjects are relatively naïve to common infections.
Because exposure to other common viruses does not differ between paediatric MS patients and controls, the findings suggest that the association between MS and EBV may be specific, Dr. Banwell said.
The study was supported by a grant from The Hospital for Sick Children Foundation.
[Study title: Viral Studies in Pediatric Multiple Sclerosis. Abstract:
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