Celiac disease in pediatric patients according to HLA genetic risk classes: a retrospective observational study

Abstract

Background Celiac disease (CD) is an autoimmune enteropathy in which HLA-DQ haplotypes define susceptibility. Our aim was to evaluate if belonging to a certain HLA-DQ class risk could be associated to the clinical, serological and histological presentation of CD. Methods We performed a retrospective observational monocentric study including all 300 patients diagnosed with CD, who underwent HLA typing. Clinical, serological and histological data was collected from clinical records and their association with HLA-DQ class risk was verified through statistical tests. Results In our sample mean age at onset was 6.7 ± 4.2 years, with a prevalence of females (n = 183; 61%), typical symptoms (n = 242; 80.6%) and anti-tTG IgA ≥ 100 U/mL (n = 194; 64.7%). Family history was present only in 19% (n = 57) of patients, and it was not significantly associated with any of the clinical and demographical data analyzed or the belonging to a certain HLA-DQ class risk. We found in the male population more frequently a coexistence of CD and atopic syndrome (males: n = 47; 40.2%; females: n = 50; 27.3%; p = 0.020). Early age of onset, instead, was associated with typical symptoms (m = 6.4 ± 4; p = 0.045) and elevated liver enzymes (m = 5 ± 3.8; p < 0.001), while later age of onset was associated with presence of other autoimmune diseases (m = 8.2 ± 4; p = 0.01). We observed statistically significant influences of HLA class risk on antibodies and liver enzymes levels: G1, G4 and G2 classes showed more frequently anti-tTG IgA ≥ 100 U/mL (n = 44; 80%, n = 16; 69.6%, n = 48; 67.6% respectively; p-value = 0.037), and in patients from G2 class we found enhanced liver enzymes (n = 28; 39.4%; p-value = 0.005). HLA class risk was still significantly associated with anti-tTG ≥ 100 (p = 0.044) and with hypertransaminasemia (p = 0.010) after a multiple logistic regression adjusted for the effect of gender, age at onset and family history. Conclusions We failed to prove an association between HLA-DQ genotypes and the clinical features in our CD pediatric patients. Although, our results suggest an effect of the DQB1–02 allele not only on the level of antibodies to tTG, but possibly also on liver involvement.

Extra-intestinal manifestations of Celiac disease in children: their prevalence and association with human leukocyte antigens and pathological and laboratory evaluations

“…There was also a statistically significant relation between HLA-DQ8 and both weight and height in the studied population which is because of two-year age difference of these group (reflecting age difference). This may concordant with a previous study in which has been linked to as age at onset of CD and HLA typing [ 14 ], however, in a recent study failed to link a relation between age of onset, sex, Marsh class and HLA types, while hypertransaminasemia and levels of anti-tTG were significantly affected by HLA typing [ 34 ]. There was not any statistically significant association between HLAs and anti-tTG titer in our population.…”

“…Our findings are consistent with a review of data by the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition Guidelines for Diagnosing CD 2020, which included 555 asymptomatic children with IgA anti-tTG titers 10 × upper limit of normal and who had diagnostic small bowel biopsies, with 94.2% having Marsh class 2 or 3 duodenal lesions [ 35 ]. In our study, most of studied HLA types including DQ2, DQ6, DQ8 are significantly associated with the histopathological classification of CD at the time of diagnosis which is concordant with previously mentioned review and inconsistent with a recent study [ 33 , 34 ]. However, we found no significant difference between the presence of EIM in CD and compliance with a GFD, sex, Marsh class, or levels of IgA anti-tTG.…”

Liver abnormalities in celiac disease and response to gluten free diet: A systematic review and meta‐analysis

“…A detailed flow of the studies included in the meta‐analysis is shown in figure 1 (PRISMA figure). The details of the included studies are shown in Table 1 17–67 . Excluded studies with reason of exclusion are shown in Table S2.…”

UK NEQAS and BSHI guideline: Laboratory testing and clinical interpretation of HLA genotyping results supporting the diagnosis of coeliac disease

“…Over 99% of patients with CD possess specific HLA-DQA1 and DQB1 genes that encode the CD-associated heterodimer proteins DQ2 and/or DQ8 (Megiorni et al, 2012;van Heel et al, 2007;Wolters et al, 2008). Approximately 90% of individuals with CD, across all populations, express either HLA-DQ2 and/or -DQ8 molecules with less than 2% of CD patients lacking these HLA types completely (Brown et al, 2019;De Silvestri et al, 2018;Tolone et al, 2021).…”