Autoimmune responses to the beta cell autoantigen, insulin, and the INS VNTR-IDDM2 locus

Clin Exp Immunol. 1998 Dec;114(3):370-6. doi: 10.1046/j.1365-2249.1998.00744.x.


Type 1 diabetes is associated with autoimmunity to insulin. Genetic susceptibility to type 1 diabetes is polygenic and includes the INS VNTR-IDDM2 locus which may regulate the expression of insulin in pancreas and thymus. In order to determine whether insulin autoimmunity could be attributed to a genetic susceptibility conferred by the INS VNTR-IDDM2 locus, peripheral blood T cell proliferation to human insulin and insulin autoantibodies (IAA) was measured in patients with new onset type 1 diabetes and control subjects. IAA were detected in 21 of 53 patients and in none of 25 control subjects, while T cell responses were low (stimulation index range 0.4-7.2) and similar in both groups. Both antibody and T cell responses were higher in younger subjects and IAA were more prevalent in patients with the HLA-DR4 allele. No relationship was observed between humoral and cellular responses to insulin. No association was found between the INS VNTR-IDDM2-susceptible allele and insulin autoimmunity. Increased T cell responses and IAA were found in patients with either the diabetes-susceptible or the diabetes-protective INS VNTR-IDDM2 locus genotypes, and increased T cell responses were also found in control subjects with either susceptible or protective INS VNTR-IDDM2 locus genotypes. This study confirms that primary T cell proliferative responses to insulin are low and detectable also in control subjects. The detection of T cell proliferation and autoantibodies to insulin in subjects with and without the protective INS VNTR-IDDM2 locus genotypes does not support the hypothesis of an allele-specific capacity for tolerance induction which could determine a susceptibility to develop autoimmunity against the insulin protein and subsequently diabetes.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Antibody Formation / immunology
  • Autoantigens / genetics
  • Autoantigens / immunology
  • Autoimmunity*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • HLA-DR3 Antigen / genetics
  • HLA-DR3 Antigen / immunology
  • HLA-DR4 Antigen / genetics
  • HLA-DR4 Antigen / immunology
  • Humans
  • Immunity, Cellular / immunology
  • Infant
  • Insulin / genetics
  • Insulin / immunology*
  • Islets of Langerhans / immunology*
  • Male
  • Middle Aged
  • Minisatellite Repeats


  • Autoantigens
  • HLA-DR3 Antigen
  • HLA-DR4 Antigen
  • Insulin