Repeated Screening Can Be Restricted to At‐Genetic‐Risk Birth Cohorts

Björck, S; Lynch, Kristian; Brundin, Charlotte; Agardh, Daniel

doi:10.1097/mpg.0000000000000946

Cited by 25 publications

(31 citation statements)

References 30 publications

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“…This two‐step CD‐screening approach is especially important in high‐risk groups (such as family members of a patient with CD, individuals with an autoimmune disease such as type 1 diabetes, and certain conditions associated with CD, eg, Down and Turner syndromes). Some researchers have taken this two‐step approach further and propose using the HLA‐DQ molecular test as a first step in the mass screening of the general population for CD . Based on our study, 39% of our patient population is genetically susceptible to developing CD, and consequently, the two‐step approach would be much less cost‐effective than a one‐step approach (ie, screening with TTG‐IgA).…”

Section: Discussionmentioning

confidence: 71%

“…4,13 In clinical practice, many two-step approach further and propose using the HLA-DQ molecular test as a first step in the mass screening of the general population for CD. [16][17][18][19] Based on our study, 39% of our patient population is genetically susceptible to developing CD, and consequently, the two-step approach would be much less cost-effective than a onestep approach (ie, screening with TTG-IgA). The cost-effectiveness of the two-step approach is dependent on the frequency of the HLA risk alleles in the studied population.…”

Section: Discussionmentioning

confidence: 90%

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HLA‐DQ genotypes relative risks for celiac disease in Arabs: A case‐control study

Al–Hussaini

Eltayeb‐Elsheikh

Alharthi

et al. 2019

J of Digest Diseases

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Objectives It remains unknown what degree of risk is conferred by celiac disease (CD)‐predisposing human leukocyte antigen (HLA)‐DQ genotypes in Saudi Arabia compared with in Western countries. In this study, we aimed to determine the CD risk gradient associated with the HLA‐DQ genotypes and to compare HLA‐DQ genotypes between symptomatic patients with CD and screening‐identified asymptomatic CD patients. Methods We enrolled three groups of subjects, including 46 CD children diagnosed consecutively over the past 10 years, 54 CD children diagnosed during a mass screening of schoolchildren, and 192 healthy controls. All the participants were typed for the HLA‐DQA1 and HLA‐DQB1 genes by polymerase chain reaction sequence‐specific oligonucleotide probes. Results Comparing the patients with CD to controls, we identified 5 groups in the CD risk gradient: (i) very high risk associated with the DQ2.5/DQ8 genotype (odds ratio [OR] 46.93); (ii) high risk (homozygous DQ2.5, DQ2.5/DQ2.2; OR 4.12‐5.04); (iii) intermediate risk (heterozygous DQ2.5, DQ8/DQ2.2; OR 1.61 and 1.67); (iv) low risk (DQ8, DQ2.2); and (v) very low risk (DQ2.x, DQX.5, DQX.x). Heterozygous DQ8 was more common in screening‐identified group compared to symptomatic patients (13.0% vs 2.2%); however, other genotypes were very similar between the two groups. Conclusion The highest risk of developing CD in our Saudi Arabia population is associated with the DQ2.5/DQ8 genotype.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 90%

HLA‐DQ genotypes relative risks for celiac disease in Arabs: A case‐control study

Al–Hussaini

Eltayeb‐Elsheikh

Alharthi

et al. 2019

J of Digest Diseases

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“…Finally, as mentioned in the Introduction, the most recent ESPGHAN guidelines for the diagnosis of pediatric CD significantly increased the practical usefulness of HLA typing: indeed, those introduced the possibility to achieve the final diagnosis of CD in pediatric patients without performing intestinal biopsies in selected cases showing specific clinical and serological criteria and, importantly, carrying HLA alleles encoding DQ2 and/or DQ8 heterodimers (11). Moreover, the growing interest in CD case finding strategies in at-risk groups and also in the general pediatric population might further increase the request of these genetic analyses, which are currently limited by the traditional costs of highresolution HLA typing (46,47). According to current clinical studies, most children with CD carry DQ2 and, in a lesser extent, DQ8 heterodimers; the remaining part (being DQ2 and DQ8 negative) mainly consists of children carrying one Systematic Review | De Silvestri et al…”

Section: Discussionmentioning

confidence: 99%

“…or two HLA-DQB1*02 alleles or, in a much lesser extent, only the HLA-DQA1*05 allele (coding the α chains of HLA-DQ2). Less than 1% of children affected with CD resulted to lack the aforementioned HLA alleles completely (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). Generally, HLA typing is quite expensive and, thus, new techniques to reduce its costs are being in the experimental phase (49,50).…”

mentioning

confidence: 99%

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HLA-DQ genetics in children with celiac disease: a meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ β chains

et al. 2018

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BackgroundSpecific HLA-DQ genes have been recognized as necessary - but not sufficient - factors for the occurrence of Celiac Disease (CD). Through a meta-analysis, evaluating the distribution of CD-related HLA genotypes in children, we aimed at providing insights for a potential widened screening strategy.MethodsAfter a systematic search on the association between class II HLA genes and CD in children, 46 publications were obtained and assessed for eligibility. A total of 13 eligible studies were submitted to data extraction and analysis (10 case-control studies and 3 cohort studies). Case-control studies collectively enrolled 740 CD patients and 943 controls.ResultsIn the population-stratified analysis, the following alleles conferred a significantly increased risk for CD: HLA-DQB1*02 (odds ratio [OR]=10.28) and HLA-DQB1*03:02 (OR=2.24). By drafting a risk gradient to develop CD according to HLA genetic background, the highest risk is confirmed to exist for DQ2/DQ2 homozygous subjects, regardless of the ethnicities (OR=5.4). Actually, the genotype DQ2/β2 showed basically the same risk (OR=5.3). Indeed, no differences have been found in CD risk between DQ2/β2 and DQ2/DQ2, as well as between DQ8/β2 and DQ2/DQ8, and between β2/DQX and DQ2/X.ConclusionThe HLA-DQB1*02:01 allele is present in more than 90% CD children. In the perspective of a widened pediatric population screening for CD, a double-step process might be suggested: HLA-DQB1*02:01 might be investigated first and, only if this result is positive, children might be candidate for a prospective serologic screening, as a second step.

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Longitudinal screening of HLA‐risk and HLA‐nonrisk children for celiac disease to age 15 years: CiPiS study

Boström,

Brundin,

Björck

et al. 2024

J. pediatr. gastroenterol. nutr.

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ObjectivesAutoantibodies against tissue transglutaminase (tTG) are serological markers of celiac disease. The aim was to study the applicability of human leukocyte antigen (HLA)‐genotyping and tTG autoantibodies in the screening of celiac disease in a longitudinal birth cohort followed to age 15 years.MethodsIncluded were 13,860 HLA‐DQ‐genotyped children at birth and previously invited to a screening at age 3 and 9 years, respectively. HLA‐DQB1*02 and/or DQB1*03:02 (HLA‐risk) children were compared with non‐HLA‐DQB1*02 and non‐DQB1*03:02 (HLA‐nonrisk) children. The present study reinvited 12,948/13,860 (93.4%) children at age 15 years of whom 1056/2374 (44.5%) participated in screening at both age 3 and 9 years. Both immunoglobulin A (IgA) and G (IgG) autoantibodies against tTG were analyzed separately in radiobinding assays. Persistently tTG autoantibody‐positive children were examined with intestinal biopsy to confirm the diagnosis of celiac disease.ResultsAt age 3 years, celiac disease was diagnosed in 56/1635 (3.4%) HLA‐risk children compared with 0/1824 HLA‐nonrisk children (p < 0.001). By age 9 years, celiac disease was diagnosed in 72/1910 (3.8%) HLA‐risk children compared with 0/2167 HLA‐nonrisk children (p < 0.001). Screening at age 15 years detected 14/1071 (1.3%) HLA‐risk children positive for IgA‐tTG and/or IgG‐tTG of whom 12/1071 (1.1%) remained persistently positive. Among those, 10/1071 (0.9%, 95% confidence interval: 0.4%–1.7%) HLA‐risk children were diagnosed with celiac disease compared with 0/1303 HLA‐nonrisk children (p < 0.001) and 5/491 (1.0%) were negative in screenings at both 3 and 9 years of age.ConclusionsScreening for celiac disease needs to be performed at multiple timepoints to detect all cases but can be restricted to children at HLA‐risk.

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Repeated Screening Can Be Restricted to At‐Genetic‐Risk Birth Cohorts

Abstract: Screening for CD can be restricted to children carrying HLA-DQ2 and/or DQ8. Repeated screening using tTGA is necessary to identify new patients by 9 years of age. These findings may be relevant when considering implementing screening of the general population.

Cited by 25 publications

References 30 publications

HLA‐DQ genotypes relative risks for celiac disease in Arabs: A case‐control study

HLA‐DQ genotypes relative risks for celiac disease in Arabs: A case‐control study

HLA-DQ genetics in children with celiac disease: a meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ β chains

Longitudinal screening of HLA‐risk and HLA‐nonrisk children for celiac disease to age 15 years: CiPiS study

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