Risk of Celiac Disease Autoimmunity is Modified by Non-HLA Genetic Markers During the First Year of Clinical Type 1 Diabetes Pages 58-64
Emma H. Adlercreutz1, Dorthe Hansen2, Henrik B. Mortensen3, Åke Lernmark1, Karsten Buschard4, Daniel Agardh1 and Jannet Svensson3
1Department of Clinical Sciences, Diabetes and Celiac Disease Unit, Lund University, SE-20502 Malmo, Sweden; 2Department of Paediatrics, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark; 3Department of Paediatrics, Herlev Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 4The Bartholin Institute, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
DOI: http://dx.doi.org/10.12970/2310-9971.2014.02.02.4Download PDF
Abstract: Aims: This study plotted the prevalence of celiac disease associated antibodies in relation to demographic patterns, genetic and metabolic markers during the first year after diagnosis in a multinational cohort of children with T1D.
Material and Methods: Sera from a total of 261 children (128 males, 133 females) (0.5-16.3 years) with T1D recruited at 18 European centers were screened at 1, 6 and 12 months after diagnosis, using a combined ELISA measuring both IgA and IgG antibodies against deamidated gliadin peptide and tissue transglutaminase (IgAG-DGP/tTG) and a radioligand binding assays measuring IgG-tTG. Children positive in both assays in two consecutive samples were defined as having celiac disease autoimmunity (CDA). Associations between CDA and genotypes of HLA, IL18 rap, CCR 5, PTPN2 and correlations with islet autoantibodies (ICA, GADA, IA2 and IA) and HbA1C and C-peptide were performed.
Results: At the one, six and twelve month visit after T1D diagnosis, the prevalence of IgAG-DGP/tTG across all sites were 24/238 (10.1%), 18/224 (8.0%) and 25/218 (11.5%), respectively, and 11/238 (4.6%) were confirmed positive for IgG-tTG and defined as having CDA. A subpopulation of T1D children with high levels of IgAG-DGP/tTG were defined and associated with the genotype AA of IL18RAP.
Conclusions: In our multinational cohort of children with T1D, approximately 5% were affected by CDA during first year after diagnosis of T1D. Independent of country of residence, a subpopulation being homozygote for IL18RAP were found with high levels of IgAG-DGP/tTG, indicating that non-HLA-DQ2/DQ8 genetic markers may modulate the risk for developing CDA in T1D.
Keywords: Autoimmunity, celiac disease, children, HLA, genes, type 1 diabetes Read more