title: Common viruses associated with lower pediatric multiple sclerosis risk.
abstract: BACKGROUND
  Because common viruses are encountered during childhood, pediatric multiple sclerosis (MS) offers a unique opportunity to investigate the influence of these viruses on disease susceptibility and the interactions between seroprevalence and select HLA genotypes. We studied seroprevalence for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV) type 1 and HLA-DRB1*1501/1503 status as predictors of pediatric MS.
  
  
  METHODS
  This was a retrospective analysis of prospectively collected demographic, clinical, and biologic data in subjects up to 18 years of age with early MS, control subjects seen at the same regional referral pediatric MS clinics, and additional healthy pediatric control subjects.
  
  
  RESULTS
  Patients with early pediatric MS (n=189) and pediatric control subjects (n=66) were tested. Epstein-Barr nuclear antigen-1 seropositivity was associated with an increased odds of MS (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.52-9.38, p=0.004) in analyses adjusted for age, sex, race, ethnicity, and HLA-DRB1*1501/1503 status. In multivariate analyses including EBV status, a remote infection with CMV (OR 0.27, 95% CI 0.11-0.67, p=0.004) was associated with a lower risk of developing MS. Although a remote infection with HSV-1 was not associated with an increased odds of MS, a strong interaction was found between HSV-1 status and HLA-DRB1 in predicting MS (p<0.001). HSV-1 was associated with an increased risk of MS in those without a DRB1*15 allele (OR 4.11, 95% CI 1.17-14.37, p=0.03), whereas the effect was reversed in those who were DRB1*15-positive (OR 0.07, 95% CI 0.02-0.32, p=0.001).
  
  
  CONCLUSIONS
  These findings suggest that some infections with common viruses may in fact lower MS susceptibility. If this is confirmed, the pathways for risk modification remain to be elucidated.
authors.affiliation: UCSF Regional Pediatric Multiple Sclerosis Center, 350 Parnassus Ave., Suite 908, San Francisco, CA 94117, USA. emmanuelle.waubant@ucsf.edu
authors.forename: E
authors.initials: E
authors.lastname: Waubant
authors.forename: E M
authors.initials: EM
authors.lastname: Mowry
authors.forename: L
authors.initials: L
authors.lastname: Krupp
authors.forename: T
authors.initials: T
authors.lastname: Chitnis
authors.forename: E A
authors.initials: EA
authors.lastname: Yeh
authors.forename: N
authors.initials: N
authors.lastname: Kuntz
authors.forename: J
authors.initials: J
authors.lastname: Ness
authors.forename: D
authors.initials: D
authors.lastname: Chabas
authors.forename: J
authors.initials: J
authors.lastname: Strober
authors.forename: J
authors.initials: J
authors.lastname: McDonald
authors.forename: A
authors.initials: A
authors.lastname: Belman
authors.forename: M
authors.initials: M
authors.lastname: Milazzo
authors.forename: M
authors.initials: M
authors.lastname: Gorman
authors.forename: B
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.forename: J R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: J A
authors.initials: JA
authors.lastname: James
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D015897:Comorbidity / Q000639:trends; D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006561:Herpes Simplex / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics / Q000821:virology*; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; C489631:HLA-DRB1*15:01 antigen