Copyright
©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Targeted genotyping for the prediction of celiac disease autoimmunity development in patients with type 1 diabetes and their family members
Maureen M Leonard, Stephanie Camhi, Victoria Kenyon, Rebecca A Betensky, Craig Sturgeon, Shu Yan, Alessio Fasano
Maureen M Leonard, Stephanie Camhi, Victoria Kenyon, Craig Sturgeon, Shu Yan, Alessio Fasano, Mucosal Immunology and Biology Research Center, Mass General Hospital for Children, Boston, MA 02115, United States
Maureen M Leonard, Stephanie Camhi, Victoria Kenyon, Craig Sturgeon, Shu Yan, Alessio Fasano, Center for Celiac Research and Treatment, Mass General Hospital for Children, Boston, MA 02115, United States
Maureen M Leonard, Stephanie Camhi, Victoria Kenyon, Craig Sturgeon, Shu Yan, Alessio Fasano, Department of Pediatric Gastroenterology and Nutrition, Mass General Hospital for Children, Boston, MA 02114, United States
Rebecca A Betensky, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States
Author contributions: All authors contributed to writing the manuscript and reviewing the manuscript.
Supported by The Center for Celiac Research and Treatment, The Nutrition Obesity Research Center at Harvard, No. P30-DK04561; to MML and RAB and The Harvard Clinical and Translational Science Center, the Harvard Catalyst, NCRR and NCATS, NIH Award, No. UL1 TR001102.
Institutional review board statement: All study procedures were reviewed and approved by the Partners Human Research Committee Institutional Review Board (IRB).
Informed consent statement: All patients signed informed consent for the investigations carried out.
Conflict-of-interest statement: The authors declare no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items
Data sharing statement: Data can be provided on request by the corresponding author.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Maureen M Leonard, MD, MSc, Instructor, Clinical Director, Department of Pediatric Gastroenterology, Mass General Hospital for Children, 55 Fruit Street (Jackson 14), Boston, MA 02114, United States. mleonard7@mgh.harvard.edu
Telephone: +1-617-7244155
Received: February 6, 2019
Peer-review started: February 9, 2019
First decision: February 19, 2019
Revised: March 4, 2019
Accepted: March 8, 2019
Article in press: March 9, 2019
Published online: March 15, 2019
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 genotype. We 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.
Core tip: Serological screening for celiac disease (CD) autoimmunity in subjects with type 1 diabetes (T1D) and their first-degree relatives (FDRs) found an underestimation of CD by 2 fold in T1D patients and 2.8 fold in their FDRs. Participants with T1D who carry DR7-DQ2/DR4-DQ8 were more likely to screen positive for CD autoimmunity. There was no association between carrying zonulin genetics and an increased risk of developing CD in our cohort. Patients with T1D and their FDRs have an increased risk of developing CD compared to the general population and, given the often-asymptomatic nature of disease, physicians should have a low threshold for screening.
