HLA-DQ typing in the diagnostic algorithm of celiac disease

Abstract

Objective: celiac disease (CD) is an immune-mediated chronic inflammatory disease associated with HLA-DQ2 and DQ8 molecules. We evaluated the role of HLA in the CD diagnostic algorithm in order to contribute to the development of practical indications for the use of HLA typing.Material and methods: we selected 317 subjects typed for DR-DQ genes. CD was present in 123 patients, and 89 were included in the study; a control sample of 70 healthy individuals was recruited.Results: 64% of patients with CD carried DQ2 heterodimer (a5b2), 13.5% carried DQ8 heterodimer without DQ2, 21.4% only showed b2 chain and 1.1% were positive for DQ2 a5 chain. The only presence of a5 chain did not predispose to CD, while DQB1*02 allele resulted more frequent than in other reports, pointing out the intrinsic correlation between b2 chain and CD. In the case-control study we observed a progression of increased risk, ranging from 1:7 for HLA-DQ2 homozygous to 1:85 for DQ8 heterozygous subjects. Overall, 8,6% of first degree family members were affected, exclusively in presence of HLA-DQ2, -DQ8 or DQB1*02, and CD was significantly more frequent among siblings than parents. Finally, considering the different patterns of clinical presentation among the HLA-DQ risk classes identified we found no relationship between CD clinical presentation and HLA-DQ risk categories.Conclusions: our results strengthen the evidence that HLA-DQ status strongly influences the development of CD and demonstrate that knowledge of a patient's HLA-DQ genotype allows to establish clinically relevant genetic risk profiles.

Celiac disease and HLA-DQ genotype: diagnosis of different genetic risk profiles related to the age in Badajoz, southwestern Spain

“…As expected, and according to other authors (15,25,(30)(31)(32)(33)(34), the DQ2 homozygous status (category XIV) had the highest risk for CD (1:10 in children and adults patients); next in risk level were the DQ2 heterozygous categories with no DQ8 (XI, XII and V); categories with DQ8 in homozygosis or heterozygosis with DQB01*02 (VII, X and VIII) had a lower risk. When we analyzed celiac children and adults separately, the risk was different.…”

“…There are several studies that demonstrate that isolated DQB1*02 would confer a predisposition towards triggering CD (15,25,26,30,31,(36)(37)(38)(39), and the presence of isolated DQA1*05 would not (15,22,25). In our study, 1 % of celiac children and 1.4 % of adults presented isolated DQB1*02 compared to healthy controls (11.1 % of cases).…”

“…As described in other studies, the most prevalent genotype in celiac patients was the DQA1*05 (x 1 copy), DQB1*02 (x 1 copy), DQB1*0302 (x 0 copies) (category V: 34.1 %) (15,25,29).…”

“…Our results were consistent with previous studies of celiac children in Spain (20), Northern Europe (12,24), and the United States (8). However, they did not correspond to The European Genetics Cluster on Celiac Disease, which observed less DQ2 positive patients in Southern Europe than in Northern (84.5 vs. 90.2 %) (25,26).…”

Does dermatitis herpetiformis result in bone loss as coeliac disease does?: a cross sectional study

“…Interestingly, males have a higher prevalence of DH (1.5-2:1) unlike CD (1:2-4) (3). Both diseases show strong genetic predisposition: the incidence of DH and CD among first-degree relatives is about 15 times higher than in the general population (4), and a close association between DH and human leukocyte antigen-DQ2 or DQ8 (5,6) has been reported, such as in CD (7).…”