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Infections with CMV and, in those carrying a HLA-DRB1*15 allele, HSV-1, are protective from pediatric MS

for the US Pediatric MS Network

Background

As common viruses are encountered during childhood, pediatric multiple sclerosis (MS) offers a unique opportunity to more closely investigate the influence of these viruses on disease susceptibility and the interactions between viral seroconversion and select HLA genotype.

Aim of the study To determine whether seroconversion with Epstein-Barr virus (EBV), cytomegalovirus (CMV), or herpes simplex virus (HSV)-1 or -2 is associated with a greater risk of developing MS in children and whether the presence of HLA-DRB1*1501 or 1503 influences this risk, either independently or in an interactive fashion with these viruses.

Methods

  • Patients <18 years at MS onset were recruited at six Regional Pediatric MS Centers sponsored by the National MS Society (NMSS) (UCSF, SUNY at Stony Brooks, SUNY at Buffalo, UAB, Harvard, Mayo Clinic). The control group included pediatric patients seen at the same clinics during the same period for whom CIS or MS was ruled out and healthy pediatric individuals recruited for a prior study.
  • Batched EBV, CMV, and HSV-1 and -2 assays (IgG) were performed blindly at the Oklahoma Medical Research Foundation (Dr J.A. James) with normalized ELISAs.
  • All DNA samples were typed with SNPs for the presence of HLADRB1*1501/1503 (Dr. J. Oksenberg, UCSF).

Statistical analysis

Multivariate analysis using logistic regression was performed, adjusted for age, sex, race, ethnicity and DRB1 status, to evaluate if children who were seropositive for each virus or for DRB1 were more likely than others to have pediatric MS. Interactions were assessed by generating an interaction term for each virus (positive or negative) and DRB1 status.