HLA-DR15 is associated with lower age at onset in multiple sclerosis

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Published on: July 14, 2016

T Masterman1, A Ligers, T Olsson

  • 1Department of Neurology, Karolinska Institutet at Huddinge University Hospital, Sweden.

Annals of Neurology
|August 12, 2000
PubMed

Insights

Human Leukocyte Antigen (HLA) genes DR15 and DR17 are associated with multiple sclerosis (MS) susceptibility. However, HLA-DRB1 alleles do not impact MS disease course or severity, though DR15 carriers may develop MS earlier.

Area of Science:

  • Immunogenetics
  • Neuroimmunology
  • Human Genetics

Background:

  • Multiple sclerosis (MS) is a chronic neurological disease with a complex etiology.
  • Human Leukocyte Antigen (HLA) genes are known to influence MS susceptibility, but previous studies had small sample sizes.
  • Consistent patterns regarding HLA gene impact on MS clinical course and severity have been lacking.

Purpose of the Study:

  • To investigate the impact of HLA-DRB1 alleles on the clinical course and disease severity in MS.
  • To compare the frequencies of the DR15 susceptibility allele in various clinicodemographic subgroups of MS patients.
  • To identify novel HLA associations with MS susceptibility using the largest dataset to date.

Main Methods:

  • Genotyping of HLA class II alleles in 948 MS patients.
  • Cataloguing of clinical and demographic data for all participants.
  • Statistical analysis to correlate HLA genotypes with MS susceptibility, clinical course, and disease severity.

Main Results:

  • HLA-DR17, in addition to DR15, is positively associated with MS susceptibility.
  • No investigated HLA-DRB1 alleles were found to influence the clinical course or outcome of MS.
  • DR15 carriers were found to develop MS at an earlier age compared to non-carriers.
  • DR15 positivity rates varied across diagnostic categories, potentially reflecting phenocopy contamination.

Conclusions:

  • HLA-DR15 and DR17 are confirmed as susceptibility alleles for MS.
  • HLA-DRB1 alleles do not appear to be determinants of MS disease progression or severity.
  • Early-onset MS is associated with DR15 carriage.
  • Further research is needed to understand the role of HLA in MS pathogenesis and to refine diagnostic criteria.

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