Autoantibodies to GAD, IA-2 and insulin in ICA-positive first-degree relatives of children with type 1 diabetes: a comparison between parents and siblings

• Published in: Diabetes/metabolism research and reviews Vol. 18; no. 1; pp. 43 - 48
• Main Authors: Korhonen, Sari, Knip, Maria M., Kulmala, Petri, Savola, Kaisa, Åkerblom, Hans K., Knip, Mikael
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2002; Wiley
• Subjects: Autoantibodies - blood; Biological and medical sciences; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glutamate Decarboxylase - immunology; glutamic acid decarboxylase; Hormones. Endocrine system; IA-2; Insulin - immunology; insulin autoantibodies; islet cell antibodies; Islets of Langerhans - immunology; Medical sciences; Nuclear Family; Parents; Pharmacology. Drug treatments; Regression Analysis; relatives; type 1 diabetes; Endocrinopathy; Human; Immunopathology; Glutamic acid; Decarboxylase; Prevalence; Enzyme; Parent; Autoantibody; Autoimmune disease; Lyases; Sibling; Epidemiology; Insulin; Protein; Antigen; Carbon-carbon lyases; Autoantigen; Carboxy-lyases; Insulin dependent diabetes; Islet cell antibody; Immunofluorescence; Child; Comparative study
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.258

Background Islet cell antibodies (ICA) represent a heterogenous group of autoantibodies to diabetes‐associated antigens, including glutamic acid decarboxylase (GAD) and the IA‐2 protein. The objectives of the present study were to compare the prevalence of autoantibodies to known biochemically characterized autoantigens between ICA‐positive non‐diabetic parents and siblings of children with type 1 diabetes and to evaluate how such antibodies explain ICA reactivity. Methods The presence and levels of GAD antibodies (GADA), IA‐2 antibodies (IA‐2A) and insulin autoantibodies (IAA) were analyzed in the sera of 184 ICA‐positive first‐degree relatives (79 parents and 105 siblings). Results The prevalences of GADA (61.9% in siblings vs 32.9% in parents), IA‐2A (55.2% vs 15.2%) and IAA (41.0% vs 0%) were increased among ICA‐positive siblings relative to ICA‐positive parents (p<0.001). The siblings had higher ICA titers (p<0.001) than the parents but tended to have lower GADA levels (p=0.12). IA‐2A levels did not differ between the two groups. IA‐2A levels explained a higher proportion of the ICA reactivity in the siblings than in the parents (44% vs 12%, p=0.004), and GADA levels had the same tendency (27% vs 10%, p=0.11). In a multiple regression analysis, GADA and IA‐2A were found to explain together 16% of the ICA reactivity in parents and 49% in siblings (p=0.003 for the difference). Conclusions These results indicate that the increased frequency of additional diabetes‐associated autoantibodies in ICA‐positive siblings when compared to their ICA‐positive parents may reflect the increased risk of progression to clinical type 1 diabetes previously reported in young ICA‐positive relatives. We conclude that ICA immunofluorescence is not only due to GADA and IA‐2A, but there are other additional antigens contributing to the ICA reactivity. Antibodies to such antigens appear to be more common among adults than in children. Copyright © 2002 John Wiley & Sons, Ltd.