The HLA-DR phenotype modulates the humoral immune response to enterovirus antigens

Diabetologia. 2003 Aug;46(8):1100-5. doi: 10.1007/s00125-003-1157-x. Epub 2003 Jul 5.


Aims/hypothesis: Enterovirus infections are among the environmental risk factors potentially contributing to the pathogenesis of Type 1 diabetes. The aim of this study was to evaluate virus-host interaction by analysing the enterovirus antibody levels in subjects carrying different HLA-DR alleles associated with either increased or decreased risk of Type 1 diabetes.

Methods: Antibodies against coxsackievirus B4 were measured to study immune responses induced by natural enterovirus infections and against poliovirus 1 to study immune responses induced by immunisation by enterovirus antigens (vaccine). Antibodies against the mumps virus were measured as a control. Study subjects included siblings of children with Type 1 diabetes taking part in the Childhood Diabetes in Finland (DiMe) Study and carrying either HLA-DR risk (DR3 and/or DR4) or protective (DR2) alleles.

Results: Children with either the HLA-DR3 or HLA-DR4 allele and those with both these risk alleles had higher Coxsackie B4 antibody levels than children carrying the HLA-DR2 allele ( p=0.01, p=0.01 and p=0.008, respectively). High responders (IgG levels higher than 75 percent) were also more frequent among genetically susceptible children compared to children with the protective DR2 allele (27% vs 12%) ( p<0.009). The same trend was seen for poliovirus antibodies, while mumps antibody levels had a different pattern (high responders more common among DR2-positive subjects).

Conclusions/interpretation: Diabetes-associated HLA-DR risk alleles were associated with a strong immune responsiveness and protective alleles with a weak responsiveness against enterovirus antigens. This phenomenon should be taken into consideration in serological case-control studies and it might play a role in virus-induced beta-cell damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation
  • Antigens, Viral / blood
  • Antigens, Viral / immunology*
  • Child
  • Diabetes Mellitus, Type 1 / immunology*
  • Enterovirus / immunology*
  • Enterovirus Infections / immunology*
  • Female
  • Genetic Predisposition to Disease / genetics
  • HLA-DR Antigens / genetics*
  • Heterozygote
  • Homozygote
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Male
  • Mumps virus / immunology
  • Phenotype
  • Siblings
  • Sweden


  • Antigens, Viral
  • HLA-DR Antigens
  • Immunoglobulin A
  • Immunoglobulin G