Familial clustering of β-cell autoimmunity in initially non-diabetic children

• Published in: Diabetes/metabolism research and reviews 2006-01, Vol.22 (1), p.53-58
• Main Authors: Kukko, Marika, Toivonen, Anna, Kupila, Antti, Korhonen, Sari, Keskinen, Päivi, Veijola, Riitta, Virtanen, Suvi M., Ilonen, Jorma, Simell, Olli, Knip, Mikael
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Autoantibodies - blood; autoantibody; Autoimmunity - genetics; 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; Female; general population; Genetic Predisposition to Disease; Genotype; Glutamate Decarboxylase - immunology; HLA-DQ Antigens - genetics; HLA-DQ beta-Chains; HLA-DQB1; Humans; ICA; Infant; Infant, Newborn; Insulin - immunology; Islets of Langerhans - immunology; Male; Medical sciences; risk assessment; sibling
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.584

Background Type 1 diabetes is characterised by familial aggregation. We set out to explore whether β‐cell autoimmunity, which is considered to precede clinical disease, also shows familial clustering. Methods Tests for HLA DQB1 alleles (*02, *0301, *0302, *0602) and islet cell autoantibodies (ICA) were performed on 5836 children from 2283 families. When a child tested positive for ICA, all his/her previous or subsequent samples that were available were also tested for insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase (GADA) and antibodies to the IA‐2 protein (IA‐2A). Results Forty‐four families were observed to have two or more children positive for at least ICA. This proportion (1.9%) was almost five times higher than expected (0.4%; p < 0.001). The frequency of multiple (≥2) autoantibodies also showed familial aggregation, the observed proportion (0.39%) being three times that expected (0.13%; p < 0.001). In 72.7% of the families with at least two ICA‐positive siblings, the children with autoantibodies had the same HLA DQB1 genotype. The median age difference between the ICA‐positive children within the same family was 3.3 years (range 0.0‐10.5 years), and the median time interval in the appearance of ICA within the family was 1.6 years (range 0.0‐3.2). Conclusions β‐cell autoimmunity, as defined by the appearance of ICA, demonstrates familial aggregation, although the antibodies do not appear in close temporal proximity or at an identical age within the same family. The HLA‐DQB1 genotypes are more often identical in siblings with autoantibodies than in other siblings. Copyright © 2005 John Wiley & Sons, Ltd.