Unit:
Κατεύθυνση ΒιοστατιστικήLibrary of the School of Health Sciences
Author:
Emmanouilidou-Fotoulaki Elpida
Supervisors info:
Βασιλική Μπενέτου, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Αναστασία Βασιλική Σύψα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Περικλής Μακρυθανάσης, Επίκουρος Kαθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Συσχέτιση Αντιγόνων Ιστοσυμβατότητας τάξης II με φαινοτυπικά χαρακτηριστικά κατά τη διάγνωση κοιλιοκάκης σε παιδιατρικό πληθυσμό της Ελλάδας
Translated title:
Association of class II histocompatibility antigens with phenotypic characteristics at diagnosis of celiac disease in pediatric population of Greece
Summary:
Introduction: Celiac disease or gluten hypersensitivity enteropathy is an autoimmune systemic disorder characterized by damage to the small intestine (enteropathy). The disease affects genetically predisposed individuals after dietary exposure to gluten and other dietary prolamins. It shows an increasing prevalence in recent years which is estimated around 1% worldwide. The clinical phenotype of the disease shows great heterogeneity and although the genetic background is extensively studied, the correlation of genetic factors and clinical features is not fully understood.
Aim: The main purpose of this study was to determine the distribution of alleles in children with celiac disease considering probable differences depending on the presence of a positive family history, to investigate the correlation between the HLA genotype and the age of diagnosis as well as the estimated risk for different forms of the disease at diagnosis or for another autoimmune disease. Finally, the possible effect of homo- or heterozygosity in specific alleles on the age of onset as well as on the phenotypic variance of the disease will be evaluated.
Materials and Methods: Data from 232 children with histologically confirmed celiac disease based on current guidelines of European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), patients at the Outpatient Clinic of Pediatric Gastroenterology of the 4th Pediatric Clinic of Aristotle University of Thessaloniki (AUTh) at the General Hospital of Thessaloniki Papageorgiou from the foundation of the clinic until June 2023 were retrieved from the medical records. Based on genotype, patients were assigned to risk groups for developing celiac disease and comparisons of remaining characteristics were made by genotypic risk group. Clinical phenotype at diagnosis, presence of iron deficiency or other autoimmune disease were used as dependent variables in univariable and multivariable regression models.
Results: Most frequent alleles were HLA- DQA1 *05 (51.07%) and HLA- DQB1 *02 (48.06%) and the haplotype DQ2.5 (34.27%) respectively. Most patients (68.93%) had intermediate genotypic risk for celiac disease while 5 patients, negative for DQ2 and DQ8, developed the disease and carried at least one DQA1 05 chain (DQ7.5 haplotype). The genotypic risk groups did not differ according to the existence of a first-degree relative with celiac disease (Fisher's exact p-value=0.52). The main symptom that most often led to the diagnosis was failure to thrive (25.43%) followed by iron deficiency (14.66%), while 26 children (11.21%) were screened for a positive family history of celiac disease. Nevertheless, clinical features at diagnosis did not appear to differ according to genotypic risk. In addition, age at diagnosis, clinical phenotype (classic/non classic), occurrence of iron deficiency, and presence of autoimmune disease did not vary across the different genotypic risk groups for celiac disease in univariable correlations and in multivariable logistic regression models. The mean age of diagnosis was 1.6 years (95% CI 1.02, 2.19, p-value=0.010) greater in patients with comorbidity and 2.12 years (95% CI 1.4, 2.84, p-value=0.005) greater in patients with an autoimmune disease. Finally, homozygosity or heterozygosity in specific alleles (DQA1 *05, DQB1 *02) was not associated with clinical parameters.
Conclusion: The results of the present study fail confirm any association between genotype and clinical characteristics at the diagnosis of celiac disease. On the contrary, the study confirms the current literature about the HLA identity of celiac disease patients and the distribution of specific alleles and haplotypes among them. Finally, it highlights the role of HLA DQ7.5 haplotype among HLA DQ2 and DQ8 negative patients reinforcing the view that the existence of a DQ a5 chain alone is sufficient to constitute a high-risk genotype for celiac disease.
Main subject category:
Health Sciences
Keywords:
Celiac disease, HLA, Pediatrics, Greece, Genotype
File:
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Emmanouilidou Fotoulaki Elpida MSc.pdf
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File access is restricted until 2026-06-19.
