ESPE Abstracts (2019) 92 FC1.5

FADES: A Birth Cohort to Understand the Mechanisms Underlying Accelerated Onset of Autoimmunity in Children with Down's Syndrome

Georgina Williams1, Georgina L. Mortimer2, Sam D. Leary3, Alistair J.K. Williams2, Kathleen M. Gillespie2, Julian P. Hamilton - Shield3


1Nutrition theme of NIHR Bristol Biomedical Research Centre (BRC), Chippenham, United Kingdom. 2Translational Health Sciences, Bristol Medical School, Faculty of health Sciences, Bristol, United Kingdom. 3Nutrition theme of NIHR Bristol Biomedical Research Centre (BRC), Bristol, United Kingdom


Background and Aims: Children with Down's syndrome (DS) are at increased risk of autoimmune conditions including type 1 diabetes (T1D), coeliac and thyroid disease. We previously examined the clinical and immunogenetic characteristics of these conditions in children with DS. An earlier age-of-onset of diabetes was observed compared with children with T1D from the general population despite having decreased frequencies of the established genetic susceptibility factors for T1D. In order to understand the mechanisms underlying accelerated onset of autoimmune diabetes and other forms of autoimmunity in children with DS, we initiated a UK wide birth cohort FADES (Feeding and Autoimmunity in Down's syndrome Evaluation study) to examine the longitudinal development of factors related to autoimmunity in these children.

Material and Methods: Infants with DS were recruited under 8 months of age. Parents completed medical and feeding questionnaires at initiation, 6 and 12 months and annually thereafter. Questionnaires included information about medical conditions, infections, antibiotic use and early feeding weaning. Mouth brushes were collected for DNA. Longitudinal urine samples were collected for Urinary C-Peptide Creatinine Ratio (UCPCR) and metabolomics, stool samples for gut microbiome and blood samples for autoantibodies. HLA susceptibility was analysed by PCR-SSP, and UCPCR by electrochemiluminescence. Serum samples were analysed for autoantibodies by radioimmunoassay.

Results: Recruitment is ongoing. To date, 95 UK infants with DS (Male n=49) have been consented; mean age at recruitment 18.4 weeks (S.D.10 weeks). Initial questionnaires have been completed by 88% of participants and at one year old by 66%; 64 participants are now over 2 years of age. Initial DNA, urine, stool and blood samples have been obtained from 77%. Of 60 children tested to date, 37% have at least one of the high risk HLA genotypes DR4-DQ8 or DR3-DQ2 for T1D. No participant has been diagnosed with T1D and this is confirmed by Urinary C peptide levels in the normal range at 1 year. Insulin autoantibody screening is ongoing; 43 participants were negative at age 2 years. Two children have developed thyroid abnormalities but are negative for thyroid peroxidase antibodies. One child, homozygous for HLA DR3-DQ2 was positive for autoantibodies to tissue transglutaminase at age 1 year consistent with a diagnosis of coeliac disease by ESPGHAN guidelines but was not diagnosed clinically until age 4.

Conclusions: FADES is the first and largest DS birth cohort to study the longitudinal development of the factors associated with autoimmunity in this high risk population.

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