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Review
. 2020 Aug 25;20(9):47.
doi: 10.1007/s11892-020-01318-8.

Early Onset of Autoimmune Diabetes in Children with Down Syndrome-Two Separate Aetiologies or an Immune System Pre-Programmed for Autoimmunity?

Georgina L Mortimer  1 , Kathleen M Gillespie  2
Affiliations
Review

Early Onset of Autoimmune Diabetes in Children with Down Syndrome-Two Separate Aetiologies or an Immune System Pre-Programmed for Autoimmunity?

Georgina L Mortimer et al. Curr Diab Rep. .

Abstract

Purpose of review: An 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 findings: Diagnosis 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. Autoimmunity 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.

Keywords: Autoimmunity; Down syndrome; HLA; Islet autoantibodies; Type 1 diabetes (T1D).

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Chromosome 21. The Down’s syndrome critical region (DSCR) and genes that may be linked to the increased risk of autoimmunity in DS are indicated
See this image and copyright information in PMC

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