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

• Published in: Diabetologia Vol. 39; no. 10; pp. 1223 - 1226
• Main Authors: GENOVESE, S, BONFANTI, R, BAZZIGALUPPI, E, LAMPASONA, V, BENAZZI, E, BOSI, E, CHIUMELLO, G, BONIFACIO, E
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-10-1996
• 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; Endocrinopathy; Autoimmunity; Human; HLA-System; Enzyme; Antibody; HLA-DR-System; Phosphoric monoester hydrolases; Autoantibody; Esterases; Lyases; Glutamate decarboxylase; Carbon-carbon lyases; Phenotype; Carboxy-lyases; Insulin dependent diabetes; Hydrolases; Protein-tyrosine-phosphatase
• ISSN: 0012-186X; 1432-0428
• 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.