Frequency of celiac disease and distribution of HLA-DQ2/DQ8 haplotypes among siblings of children with celiac disease

Abstract

BACKGROUND Celiac disease (CD) is a multifactorial disease, but genetic factors play a major role in its etiology. It has been known that human leucocyte antigen (HLA)-DQ2/DQ8 haplotypes are one of the most important predisposing genetic factors. The risk of developing CD in first-degree relatives and especially siblings of celiac patients is quite high because of having the same HLA haplotypes. AIM To evaluate the frequency of CD and the distribution of the HLA-DQ2/DQ8 haplotypes in siblings of celiac patients. METHODS Patients with biopsy-proven CD and their siblings were included in the study; those who did not have HLA genotyping were excluded from the study. All siblings were on a gluten-containing diet. The HLA genotyping, tissue transglutaminase antibody IgA antibody test, and total IgA test were performed in all participants. RESULTS A total of 57 celiac patients and their 112 siblings were included in the study. The mean age of celiac patients and siblings were 10.30 ± 3.87 years and 9.90 ± 6.11 years, respectively. HLA-DQ2/DQ8 alleles were detected in 98.2% of patients with CD and 90.2% of siblings of celiac patients. HLA-DQ genotypes were present in all siblings diagnosed with CD. Tissue transglutaminase antibody IgA test was found to be positive in 16 siblings. CD was diagnosed in 12 siblings (10.7%) by intestinal biopsy. CONCLUSION The prevalence of CD was found to be 10.7% in siblings of celiac patients in our study. One-third of the siblings diagnosed with CD were asymptomatic. We detected HLA-DQ alleles in 98.2% of celiac patients and 100% in siblings diagnosed with CD. In addition, 1 of the 2 siblings was diagnosed with CD 1 year later and the other 4 years later. Therefore, we suggest that siblings of celiac patients should be followed up with clinical findings as well as HLA analysis and serological examination. Since the risk of developing CD is much higher in asymptomatic siblings, we recommend that siblings should be screened for CD even if they are asymptomatic.

Looking for coeliac disease hiding in the family

“…Consequently, many medical practitioners actively screen individuals in these risk groups, regardless of the presence of symptoms. The prevalence of coeliac disease among first degree relatives of Australians diagnosed with the disorder is likely to be similar to rates reported overseas (at least 7.5%) 6‐8 …”

“…The rate was higher among female (8.4%) than male relatives (5.2%) and higher among siblings (8.9%) than parents (3.0%) of people with coeliac disease; it also varied by geographic location (highest in North America, lowest in South America) 7 . A more recent report found that 11% of siblings of children diagnosed with coeliac disease had the disorder 8 …”

“…Studies of focused screening of first degree relatives or other groups of people at high risk have found that many of those diagnosed with coeliac disease had no symptoms and may consequently not have been diagnosed otherwise 6‐8 . Muir and his colleagues did not report whether the first degree relatives in their study had symptoms or signs suggestive of coeliac disease 9…”

Critical COVID-19, Victivallaceae abundance, and celiac disease: A mediation Mendelian randomization study

“…Celiac disease is characterized by villous atrophy and the presence of autoantibodies targeting transglutaminase 2 (TG2), an enzyme that deamidates gluten. Human Leukocyte Antigen (HLA) genes, particularly HLA-DQ2.5, HLA-DQ 2.2, and HLA-DQ8, are recognized genetic risk factors for celiac disease [39,40]. In celiac disease patients, antigen-presenting cells express HLA-DQ molecules associated with the disease [41].…”

Celiac disease prevalence and predisposing‐HLA in a cohort of 93 Williams‐Beuren syndrome patients

“…CD is defined as an immune‐mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and characterized by a variable combination of gluten‐dependent clinical manifestations, CD‐specific antibodies (against transglutaminase TG2, endomysium and gliadin peptides) and enteropathy (Sahin, 2021). CD is the result of genetic, environmental and immune factors including specific HLA haplotypes (HLA‐DQ2 or HLA‐DQ8), gluten exposure, impaired permeability, altered immune and innate immunity leading to autoimmune susceptibility (Sahin & Mermer, 2022).…”