Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease

Choung, Rok Seon; Mills, John R.; Snyder, Melissa R.; Murray, Joseph A.; Gandhi, Manish J.

doi:10.1016/j.humimm.2020.01.006

Cited by 11 publications

(9 citation statements)

References 26 publications

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“…While the DQ haplotype has been associated with CeD in many populations, there has been controversy about the DQ2.2 haplotype, with some early studies identifying a linkage of the haplotype with CeD. A recent analysis of a large number of samples received in a clinical laboratory confirms the absence of a linkage between DQ2.2 and CeD 5 …”

Section: Discussionmentioning

confidence: 99%

“…While the HLA‐DQ type was previously determined serologically using antibodies, it is now customary to genotype HLA‐DQB1 or the HLA‐DQA1 ~ DQB1 loci and use that information to assign the serotype by imputation. HLA‐DQ heterodimer (HLA‐DQA1 ~ DQB1) typing has been used to assess CeD risk in a large sample of patients with CeD 5 . The highest risk for CeD was associated with HLA‐DQ2.5, which is formed by the HLA‐DQA1*05:XX ~ DQB1*02:01 5–8 .…”

Section: Introductionmentioning

confidence: 99%

“…HLA‐DQ heterodimer (HLA‐DQA1 ~ DQB1) typing has been used to assess CeD risk in a large sample of patients with CeD. 5 The highest risk for CeD was associated with HLA‐DQ2.5, which is formed by the HLA‐DQA1*05:XX ~ DQB1*02:01 . 5 , 6 , 7 , 8 The HLA DQ2.2 heterodimer is expressed by HLA‐DQA1*02–01 ~ DQB1*02:02 , while HLA‐DQ8 is expressed by HLA‐DQA1*03:01 ~ DQB1*03:02 .…”

Section: Introductionmentioning

confidence: 99%

“… 5 The highest risk for CeD was associated with HLA‐DQ2.5, which is formed by the HLA‐DQA1*05:XX ~ DQB1*02:01 . 5 , 6 , 7 , 8 The HLA DQ2.2 heterodimer is expressed by HLA‐DQA1*02–01 ~ DQB1*02:02 , while HLA‐DQ8 is expressed by HLA‐DQA1*03:01 ~ DQB1*03:02 . 5 The absence of the above three heterodimers has a high negative predictive value for the diagnosis of CeD.…”

Section: Introductionmentioning

confidence: 99%

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Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India

et al. 2021

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Background and Aim Human Leukocyte Antigen DQ (HLA‐DQ) genotypes play a permissive role in the genesis of celiac disease (CeD). In this case–control study, we used next‐generation sequencing to determine HLA‐DQA1 and ~DQB1 genotypes and haplotypes associated with CeD in Indian patients. Methods HLA‐DQA1 and ~DQB1 loci were amplified, using long‐range polymerase chain reaction (PCR), from DNA of 259 patients with symptomatic CeD (160 typical and 99 atypical), 45 asymptomatic CeD, 96 potential CeD, and 300 healthy adults. Amplicons were fragmented and sequenced on the Illumina platform, and alleles and haplotypes were assigned by matching against the HLA‐international ImMunoGeneTics (IMGT) database. Results HLA‐DQA1*05:01 (odds ratio [OR] 8.39, 95% confidence interval [CI] 5.64–12.47) and HLA‐DQB1*02:01 (OR 8.59, 95% CI 5.75–12.83) were the genotypes that showed a risk association with symptomatic CeD. Among the haplotypes, HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (OR 8.56, 95% CI 5.67–13.19) showed a strong risk association with symptomatic CeD. When comparing symptomatic CeD with subclinical forms (asymptomatic and potential) CeD, HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (OR 2.34, 95% CI 1.61–3.43) was significantly associated with risk of symptomatic disease. The strength of association between the HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 haplotype and the CeD phenotype showed a gradient in the order typical > atypical > asymptomatic > potential CeD. Genotypes consistent with expression of HLA DQ2 and/or 8 were noted in 128 (80%) typical, 73 atypical (74%), 27 (60%) asymptomatic, and 52 (54%) potential CeD participants. Conclusion HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (haplotype DQ2.5) showed a very strong risk association with symptomatic CeD in Indian patients. The strength of association showed a gradient of increase from potential to typical CeD, coinciding with a phenotypic change in the celiac iceberg.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India

et al. 2021

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“…Selecting an optimal screening strategy is complicated by a wide variation in the reported family risk 14‐16 possibly due to different poorly defined patient‐ and relative‐related individual factors, such as age at screening, gender, HLA haplogenotype and degree of consanquinity 1,16‐23 . Limited data on these factors make optimal timing of screening, testing of other than FDRs, and the benefits of genetic risk stratification debatable 13,15,16,23 .…”

Section: Introductionmentioning

confidence: 99%

Presence of high‐risk HLA genotype is the most important individual risk factor for coeliac disease among at‐risk relatives

Paavola

Lindfors

Kivelä

et al. 2021

Aliment Pharmacol Ther

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Summary Background Family screening has been advocated as a means to reduce the major underdiagnosis of coeliac disease. However, the precise risk of the disease in relatives and the impact of patient‐ and relative‐related individual factors remain obscure. Aims To investigate the individual risk of coeliac disease among patients' relatives. Methods Altogether 2943 relatives of 624 index patients were assessed for the presence of previous coeliac disease diagnosis, or were screened for the disease. Coeliac disease‐associated human leucocyte antigen (HLA) genotype was determined from all participants. The association between individual factors and new screening positivity was assessed by logistic regression. Results There were 229 previously diagnosed non‐index relatives with coeliac disease and 2714 non‐affected (2067 first‐degree, 647 more distant) relatives. Of these 2714 relatives, 129 (4.8%) were screening‐positive (first‐degree 5.1%, second‐degree 3.6%, more distant 3.5%). The combined prevalence of the previously diagnosed and now detected cases in relatives was 12.2% (6.3% clinically detected, 5.9% screen‐detected). In univariate analysis, age <18 years at diagnosis (odds ratio 1.60, 95% CI 1.04‐2.45) in index, and age 41‐60 years (1.73, 1.10‐2.73), being a sibling (1.65, 1.06‐2.59) and having the high‐risk genotype (3.22, 2.01‐5.15 DQ2.5/2.5 or DQ2.5/2.2 vs other risk alleles) in relatives were associated with screening positivity. Only high‐risk HLA remained significant (2.94, 1.80‐4.78) in multivariable analysis. Conclusions Unrecognised coeliac disease was common among at‐risk relatives even in a country with an active case‐finding policy, and also in relatives more distant than first‐degree. The presence of a high‐risk genotype was the most important predictor for screening positivity. ClinicalTrials.gov identifier NCT03136731.

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The HLA complex and coeliac disease

Espino

Núñez

2021

International Review of Cell and Molecular Biology

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Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease

Cited by 11 publications

References 26 publications

Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India

Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India

Presence of high‐risk HLA genotype is the most important individual risk factor for coeliac disease among at‐risk relatives

The HLA complex and coeliac disease

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