Islet Autoimmunity in Children With Down’s Syndrome

• Published in: Diabetes (New York, N.Y.) Vol. 55; no. 11; pp. 3185 - 3188
• Main Authors: Gillespie, Kathleen M., Dix, Rachel J., Williams, Alistair J.K., Newton, Richard, Robinson, Zoey F., Bingley, Polly J., Gale, Edwin A.M., Shield, Julian P.H.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.11.2006
• Subjects: Adolescent; Adult; Age; Antibodies; Autoimmune diseases; Biological and medical sciences; Celiac disease; Child; Child health; Child, Preschool; Children; Chromosome aberrations; Diabetes; Diabetes Mellitus, Type 1 - classification; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Down syndrome; Down Syndrome - genetics; Down Syndrome - immunology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Genetic aspects; Genetic Markers; Genotype; Haplotypes; Health aspects; HLA-D Antigens - genetics; Humans; Islets of Langerhans - immunology; Male; Medical genetics; Medical sciences; Population-based studies; Reference Values; Risk factors; Thyroid diseases; Type 1 diabetes; United Kingdom > UK; United States > US; Chromosomal aberration; Endocrinopathy; Human; Autoimmunity; Trisomy; Diabetes mellitus; Langerhans islet; Aneuploidy; Down syndrome; Child; Endocrine pancreas
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db06-0856

Islet Autoimmunity in Children With Down’s Syndrome Kathleen M. Gillespie 1 , Rachel J. Dix 1 , Alistair J.K. Williams 1 , Richard Newton 2 , Zoey F. Robinson 1 , Polly J. Bingley 1 , Edwin A.M. Gale 1 and Julian P.H. Shield 3 1 Diabetes and Metabolism Unit, Department of Clinical Science at North Bristol, University of Bristol, Bristol, U.K 2 Department of Neurology, Royal Manchester Children’s Hospital, Manchester, U.K 3 Division of Child Health, Department of Clinical Science at South Bristol, University of Bristol, Bristol, U.K Address correspondence and reprint requests to Dr. K.M. Gillespie, Medical School Unit, Southmead Hospital, Bristol BS10 5NB, U.K. E-mail: k.m.gillespie{at}bristol.ac.uk Abstract There is an unexplained excess of type 1 diabetes and other organ-specific autoimmune diseases in children with Down’s syndrome, but the immunogenetic characteristics of diabetes in Down’s syndrome have not been investigated. We studied the frequency of islet autoantibodies in 106 children with Down’s syndrome and no history of autoimmunity and analyzed HLA class II genotypes in 222 children with Down’s syndrome, 40 children with Down’s syndrome and type 1 diabetes, 120 age- and sex-matched children with type 1 diabetes, and 621 healthy control subjects. Co-occurrence of at least two islet autoantibody markers was observed in 6 of 106 nondiabetic children with Down’s syndrome compared with 13 of 2,860 healthy age-matched children ( P < 0.001). There was an excess of diabetes-associated HLA class II genotypes in children with Down’s syndrome and type 1 diabetes compared with age- and sex-matched healthy control subjects ( P < 0.001). Down’s syndrome children with type 1 diabetes were, however, less likely to carry the highest risk genotype DR4-DQ8/DR3-DQ2 than children with type 1 diabetes from the general population ( P = 0.01) but more likely to carry low-risk genotypes ( P < 0.0001). The frequency of subclinical islet autoimmunity is increased in Down’s syndrome, and susceptibility to type 1 diabetes in Down’s syndrome is partially HLA mediated. Other factors, possibly including genes on chromosome 21, may increase the penetrance of type 1 diabetes in Down’s syndrome. GADA, GAD antibody IA-2A, IA-2 antibody WHO, World Health Organization Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted August 10, 2006. Received June 23, 2006. DIABETES