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

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 h...

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Bibliographic Details
Published in:Diabetologia 1996-10, Vol.39 (10), p.1223-1226
Main Authors: GENOVESE, S, BONFANTI, R, BAZZIGALUPPI, E, LAMPASONA, V, BENAZZI, E, BOSI, E, CHIUMELLO, G, BONIFACIO, E
Format: Article
Language:English
Subjects:
Alleles
Autoantibodies - blood
Autoantigens - immunology
Biological and medical sciences
Child
Child, Preschool
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - immunology
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Glutamate Decarboxylase - immunology
Histocompatibility Testing
HLA-DR3 Antigen - genetics
HLA-DR4 Antigen - genetics
Humans
Immunophenotyping
Infant
Medical sciences
Membrane Proteins - immunology
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatases - immunology
Receptor-Like Protein Tyrosine Phosphatases, Class 8
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Summary: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.
ISSN:0012-186X
1432-0428
DOI:10.1007/BF02658510