title: HLA-DRB1 confers increased risk of pediatric-onset MS in children with acquired demyelination.
abstract: BACKGROUND
  Multiple sclerosis (MS) in the pediatric age group is being increasingly recognized. In adults, complex interactions between genetic and environmental factors contribute to risk and the major genetic component of MS susceptibility localizes to the major histocompatibility complex (human leukocyte antigen [HLA]). Whether HLA alleles predict MS in at-risk children presenting with acquired demyelinating syndromes (ADS) of the CNS is unknown.
  
  
  METHODS
  HLA-DRB1 alleles were typed using an allele-specific PCR amplification method on samples from 266 children presenting with ADS enrolled in the prospective Canadian Pediatric Demyelinating Disease Study and from 196 healthy controls.
  
  
  RESULTS
  Sixty-four of 266 children with ADS met established criteria for a diagnosis of MS during a mean follow-up of 3.2 ± 1.5 years. Children harboring DRB1*15 alleles were more likely to be diagnosed with MS (χ(2) = 12.2, p < 0.001; OR = 2.7), an observation strengthened by children of European ancestry (χ(2) = 10.5, p = 0.001; OR = 3.3). DRB1*15 allele frequencies in children with ADS of European ancestry subsequently diagnosed with MS were greater than in children with monophasic ADS (χ(2) = 10.7, p = 0.001) or healthy controls (χ(2) = 12.5, p < 0.001). The proportion of children with non-European ancestry diagnosed with MS was not influenced by DRB1*15 status.
  
  
  CONCLUSIONS
  DRB1*15 alleles confer increased susceptibility to pediatric-onset MS, supporting a fundamental similarity in genetic contribution to MS risk in both pediatric- and adult-onset disease. The specificity of the DRB1*15 risk allele for children with subsequent MS diagnosis, but not for all children with ADS, indicates that the risk conveyed by DRB1*15 relates to chronic CNS disease (MS), rather than acquired demyelination in general.
authors.affiliation: McGill University, Montreal Neurological Institute, Montreal, Quebec, H3A2B4, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Disanto
authors.forename: S
authors.initials: S
authors.lastname: Magalhaes
authors.forename: A E
authors.initials: AE
authors.lastname: Handel
authors.forename: K M
authors.initials: KM
authors.lastname: Morrison
authors.forename: A D
authors.initials: AD
authors.lastname: Sadovnick
authors.forename: G C
authors.initials: GC
authors.lastname: Ebers
authors.forename: B
authors.initials: B
authors.lastname: Banwell
authors.forename: A
authors.initials: A
authors.lastname: Bar-Or
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009103:Multiple Sclerosis / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D009154:Mutation; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains