Abstract
Purpose of ReviewAn increased frequency of autoimmunity in children with Down syndrome (DS) is well described but few studies have investigated the underlying mechanisms. Recent immune system investigation of individuals with DS may shed light on the increased risk of autoimmune conditions including type 1 diabetes.Recent FindingsDiagnosis of type 1 diabetes is accelerated in children with DS with 17% diagnosed at, or under, the age of 2 years compared with only 4% in the same age group in the general population. Counterintuitively, children with DS and diabetes have less human leukocyte antigen (HLA)-mediated susceptibility than age-matched children with autoimmune diabetes from the general population. Early onset of diabetes in DS is further highlighted by the recent description of neonatal cases of diabetes which is autoimmune but not HLA associated. There are two potential explanations for this accelerated onset: (1) an additional chromosome 21 increases the genetic and immunological risk of autoimmune diabetes or (2) there are two separate aetiologies in children with DS and diabetes.SummaryAutoimmunity in DS is an under-investigated area. In this review, we will draw on recent mechanistic studies in individuals with DS which shed some light on the increased risk of autoimmunity in children with DS and consider the current support for and against two aetiologies underlying diabetes in children with DS.
Highlights
Therapeutic strategies targeting the underlying mechanisms of autoimmunity may prove of great clinical value: a recent study demonstrated that autoimmune disease was the underlying or contributory cause in 3.4% of deaths in females after the first year of life [1]
It is clear that common mechanisms underlie these diseases: genome-wide association studies (GWAS) emphasise the importance of the human leukocyte antigen (HLA) and suggest roles for several T cell suppressor genes, yet mechanistic data are limited
There was an excess of diabetes-associated HLA class II genotypes in children with Down syndrome (DS) and Type 1 diabetes (T1D) compared to age and sex-matched healthy controls (p < 0.001) indicating that, as might be expected, autoimmune diabetes in DS shares the same HLA susceptibility as T1D in the general population
Summary
Therapeutic strategies targeting the underlying mechanisms of autoimmunity may prove of great clinical value: a recent study demonstrated that autoimmune disease was the underlying or contributory cause in 3.4% of deaths in females after the first year of life [1]. DS is a relatively common condition affecting over 300,000 people in the USA and 30,000 in the UK and ranging from 1:700 to 1:1000 live births [2, 3]. Those born with DS have increased risk of many complex health conditions including congenital heart defects, leukaemia, dementia and autoimmune conditions [4]. A considerably increased risk of developing clinically diagnosed type 1 diabetes (T1D) has been consistently reported in children with DS [8–11]. In a questionnaire-based study of 20,362 patients with DS in the UK and USA, the prevalence of diabetes diagnosed before age 20 in the DS population was 6 times higher
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
