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Targeted genotyping for the prediction of celiac disease autoimmunity development in patients with type 1 diabetes and their family members

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World Journal of Diabetes 2019年第3期10卷 189-199页

作者： Maureen M Leonard Stephanie Camhi Victoria Kenyon Rebecca A Betensky craig sturgeon Shu Yan Alessio Fasano Mucosal Immunology and Biology Research Center Mass General Hospital for Children Boston MA 02115 United States Center for Celiac Research and Treatment Mass General Hospital for Children Boston MA 02115 United States Department of Pediatric Gastroenterology and Nutrition Mass General Hospital for Children Boston MA 02114 United States Department of Biostatistics Harvard T.H. Chan School of Public Health Boston MA 02115 United States

BACKGROUND Patients with type 1 diabetes (T1D) and their first-degree relatives (FDRs) have an increased risk of developing celiac disease (CD) compared to the general population. This is largely explained by the shared association with major histocompatibility class II human leukocyte antigen (HLA) DQ2 and/or DQ8 between the two disease states. AIM To describe the frequency of CD autoimmunity (CDA) and the distribution of HLA and haptoglobin genotypes in patients with T1D and their FDRs. Additionally, we aimed at identifying predictors associated with an increased risk of developing CDA in patients with T1D and their family members. METHODS We obtained clinical information and blood samples from 1027 participants (302 with T1D and 725 FDRs) over a five-year period. Samples were tested for autoantibodies associated with CD, HLA-DQ alleles, and haptoglobin *** fit univariate and multiple logistic regression models for CDA separately for subjects with T1D and for FDRs of subjects with T1D. RESULTS Implementation of a screening program increased the frequency of CDA by 2- fold in participants with T1D and 2.8-fold in their FDRs. Multivariate analysis found that, in participants with T1D, having both DR7-DQ2 and DR4-DQ8 was associated with an increased frequency of CDA. In FDRs of T1D patients, reported CD in the family was associated with an increased frequency of CDA during screening. Haptoglobin 2 genotype was not associated with developing CDA in the multivariate analysis. CONCLUSION Patients with T1D and their FDRs have a high frequency of CDA. Carrying both DR7-DQ2 and DR4-DQ8 was associated with development of CDA in patients with T1D.

关键词： Screening Gluten Diabetic Coeliac Haptoglobin Human leukocyte antigen

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