HLA-DR15 In Multiple Sclerosis

  1. HLA-DRB1*1501, -DQB1*0301, -DQB1*0302, -DQB1*0602, and -DQB1*0603 Alleles are Associated With More Severe Disease Outcome on MRI in Patients With Multiple Sclerosis
    Int Rev NeuroBiol 2007;79:521-35

  2. HLA-DRB1*1501 risk association in Multiple Sclerosis may not be related to presentation of Myelin Epitopes
    J NeuroSci Res 2004 Oct 1;78(1):100

  3. No association of three polymorphisms in the alpha-2-MacroGlobulin and Lipoprotein related receptor Genes with Multiple Sclerosis
    J NeuroImmunol 2001 Aug 30;118(2):300-3

  4. Genetic susceptibility to Multiple Sclerosis: detection of polymorphic nucleotides and an intron in the 3' untranslated region of the Major Histocompatibility Complex Class II transactivator gene
    Hum Immunol 2001 Apr;62(4):371-377

  5. Additive effect of the HLA-DR15 haplotype on susceptibility to Multiple Sclerosis
    Mult Scler 2001 Apr;7(2):91-3

  6. Central MHC Gene IKBL carries a structural polymorphism that is associated with HLA-A3, B7, DR15
    ImmunoGenetics 1999 Jun 8;49(7/8):660-665

  7. Study of HLA as a predisposing factor and its possible influence on the outcome of Multiple Sclerosis in the Sanitary District of Calatayud, northern Spain
    NeuroEpidemiology 1999 Jul;18(4):203-209

  8. Major Histocompatibility Complex Class II and the course & outcome of MS: a population-based study
    Neurology 1998 Sep;51(3):742-7

  9. HLA typing in Acute Optic Neuritis
    Arch Neurol 54:76-80; Jan 1997

  1. HLA-DR15 is associated with lower age of Multiple Sclerosis onset
    Ann Neurol 2000 Aug;48(2):211-9

  2. Integrating risk factors: HLA-DRB1*1501 and Epstein-Barr virus in Multiple Sclerosis
    Neurology 2008 Mar 25;70(13 Pt 2):1113-8

  3. Human Leukocyte Antigen-DR15, low infant sibling exposure and Multiple Sclerosis: Gene-environment interaction
    Ann Neurol 2009 Sep 4;67(2):261-265


HLA-DR15 Is Associated With Lower Age Of Multiple Sclerosis Onset

Masterman T, Ligers A, Olsson T, Andersson M, Olerup O, Hillert J
Ann Neurol 2000 Aug;48(2):211-9
Karolinska Institutet at Huddinge Univ Hospital, Dept of Neurology, Sweden
PMID# 10939572; UI# 20393566

To date, more than a dozen studies have investigated the role of HLA Genes in determining clinical course and disease severity in Multiple Sclerosis (MS).

In each of these studies, however, patient sample size has been small, and no consistent pattern has emerged from the results.

For the present study, we determined HLA Class II Genotypes and catalogued clinical and demographic data for a total of 948 patients, making our data set the largest ever used to investigate HLA Genes in MS.

Our goals were both to investigate the impact of HLA-DRB1 alleles on clinical course and disease severity in MS and to compare the frequencies of the established susceptibility allele DR15 in various ClinicoDemographic subgroups of MS patients.

    We found that:

  1. In addition to DR15, DR17 is positively associated with susceptibility to MS

  2. None of the HLA-DRB1 alleles influences course or outcome in MS

  3. Carriers of DR15 are prone to MS development at an earlier age than noncarriers

  4. Differences in DR15 positivity rates, after stratification for diagnostic category and examination results:
    • Seem to reflect a gradient of phenocopy contamination, with rates increasing in proportion to the degree of:


Integrating Risk Factors: HLA-DRB1*1501 And Epstein-Barr Virus In Multiple Sclerosis

De Jager PL, Simon KC, Munger KL, Rioux JD, Hafler DA, Ascherio A
Neurology 2008 Mar 25;70(13 Pt 2):1113-8
665 Huntington Avenue, Boston, MA 02115
PMID# 18272866

Individuals with high levels of AntiBodies to the Epstein-Barr Virus Nuclear Antigen 1 (EBNA-1) have an increased risk of developing Multiple Sclerosis (MS), but this association could be confounded by genetic susceptibility.

We conducted a nested case-control study including 148 women with MS (18 with blood collected before disease onset) and 296 age-matched healthy women.

To determine whether the Human Leukocyte Antigen (HLA) DRB1*1501 allele (DR15) and Anti-Epstein-Barr Virus (anti-EBV) AntiBody Titers are independent risk factors for MS.

The association between Anti-EBNA-1 AntiBody Titers and MS risk was not affected by adjustment for DR15 and was similar in DR15-positive and DR15-negative women.

The relative risk of MS among DR15-positive women with elevated (>1:320) Anti-EBNA-1 Titers was ninefold higher than that of DR15-negative women with low (< 1:80) Anti-EBNA-1 Titers.

Anti-Epstein-Barr Virus Nuclear Antigen 1 (Anti-EBNA-1) AntiBody Titers are a risk factor for Multiple Sclerosis (MS), independently from the DR15 allele.

Carriers of the DR15 allele with elevated Anti-EBNA-1 AntiBody Titers may have a markedly increased risk of MS.



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