Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2011 Mar 1;76(9):781-6.
doi: 10.1212/WNL.0b013e31820ee1cd. Epub 2011 Feb 2.

HLA-DRB1 confers increased risk of pediatric-onset MS in children with acquired demyelination

G Disanto  1 , S Magalhaes, A E Handel, K M Morrison, A D Sadovnick, G C Ebers, B Banwell, A Bar-Or; Canadian Pediatric Demyelinating Disease Network
Collaborators, Affiliations
Comparative Study

HLA-DRB1 confers increased risk of pediatric-onset MS in children with acquired demyelination

G Disanto et al. Neurology. .

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.

Conclusion: 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.

PubMed Disclaimer

Figures

Figure
Figure
Time to multiple sclerosis diagnosis in children following acquired demyelinating syndrome (ADS) as a function of HLA-DRB1*15 status
See this image and copyright information in PMC

Comment in

References

    1. Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardieu M. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol 2007;6:887–902 - PubMed
    1. Mikaeloff Y, Suissa S, Vallee L, et al. First episode of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability. J Pediatr 2004;144:246–252 - PubMed
    1. Lincoln MR, Montpetit A, Cader MZ, et al. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nat Genet 2005;37:1108–1112 - PubMed
    1. Fogdell A, Hillert J, Sachs C, Olerup O. The multiple sclerosis- and narcolepsy-associated HLA class II haplotype includes the DRB5*0101 allele. Tissue Antigens 1995;46:333–336 - PubMed
    1. Boiko AN, Gusev EI, Sudomoina MA, et al. Association and linkage of juvenile MS with HLA-DR2(15) in Russians. Neurology 2002;58:658–660 - PubMed

Publication types

MeSH terms