Islet Autoimmunity in Children With Down’s Syndrome

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 agematched 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 ageand 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. Diabetes 55: [3185][3186][3187][3188] 2006

Down’s syndrome in diabetic patients aged <20 years: an analysis of metabolic status, glycaemic control and autoimmunity in comparison with type 1 diabetes

“…Therefore, in view of the classification proposed by the American Diabetes Association [5], it appears very likely that diabetes in young Down's syndrome patients is of the autoimmune type. Our data are in agreement with a study from the UK, which reported a higher frequency of subclinical islet autoimmunity in children with Down's syndrome [10].…”

“…It has also been suggested that diabetic patients with Down's syndrome have a lower prevalence of diabetic retinopathy [13]. This could be due to better metabolic control or a lower risk HLA genotype [10]. In our study cohort, microalbuminuria was found in 3.1% of 65 young Down's syndrome patients with diabetes after a mean of 6.1 years of diabetes duration.…”

“…This may also be due to the retrospective analysis of data, some of which were collected at a time when some or all of these antibodies were not yet known. In an extensive study of islet cell autoimmunity [10], the prevalence of diabetesassociated HLA class II genotypes was the same in diabetic patients with or without Down's syndrome. However, the frequency of the highest risk HLA class II genotypes in diabetic patients with Down's syndrome was half as high as in diabetic patients without Down's syndrome.…”

Research Article Polymorphisms of interleukin 6 in Down syndrome individuals: a case-control study.

“…It can be responsible for increased incidence of infections, mainly in the respiratory tract (Bloemers et al, 2010;Broers et al, 2012), and occurrence of autoimmune disease in DS (Gillespie et al, 2006;Pellegrini et al, 2012).…”

“…Individuals with DS present an impairment of adaptive immune system, with reduced level of lymphocytes (Kusters et al, 2009) and an increase in the susceptibility to infections and autoimmune diseases (Gillespie et al, 2006).…”