Association of IA-2 autoantibodies with HLA DR4 phenotypes in IDDM

Diabetologia. 1996 Oct;39(10):1223-6. doi: 10.1007/BF02658510.


Insulin, glutamate decarboxylase (GAD) and the protein tyrosine phosphatase-like molecule IA-2 are major targets of humoral autoimmunity in insulin-dependent diabetes mellitus (IDDM). These autoantibodies are heterogeneous with respect to age and patient human leukocyte antigen (HLA) phenotype. We have previously demonstrated that GAD and IA-2 antibodies potentially identify different subsets of IDDM patients. The aim of this study was to determine whether GAD and IA-2 autoantibodies were associated with different HLA DR phenotypes. We studied 160 patients with IDDM onset before age 16 years. At disease onset serum was tested for GAD and IA-2 antibodies by immunoprecipitation by in vitro-translated 35S-methionine labelled recombinant proteins. IA-2 antibodies were significantly associated with HLA DR4: 67 (86%) of 78 patients with HLA DR4 vs 31 (38%) of 82 non-DR4 patients had IA-2 antibodies (Pc < 0.0001) and IA-2 antibody levels were higher in patients with HLA DR4 (Pc < 0.0001). In contrast, GAD antibodies were more prevalent (Pc < 0.05) and antibody levels highest (Pc < 0.01) in patients with HLA DR3 phenotypes. These data provide further evidence that, in IDDM, production and titre of major autoantibody specificities are associated with HLA class II alleles.

MeSH terms

  • Alleles
  • Autoantibodies / blood*
  • Autoantigens / immunology*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Glutamate Decarboxylase / immunology*
  • HLA-DR3 Antigen / genetics*
  • HLA-DR4 Antigen / genetics*
  • Histocompatibility Testing
  • Humans
  • Immunophenotyping
  • Infant
  • Membrane Proteins / immunology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / immunology*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8


  • Autoantibodies
  • Autoantigens
  • HLA-DR3 Antigen
  • HLA-DR4 Antigen
  • Membrane Proteins
  • PTPRN protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase