HLA‐DQB1*02 allele in children with celiac disease: Potential usefulness for screening strategies

Poddighe, Dimitri; Capittini, Cristina; Gaviglio, Ivan; Brambilla, Ilaria; Marseglia, Gian Luigi

doi:10.1111/iji.12441

Cited by 13 publications

(17 citation statements)

References 15 publications

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“…Previously, we showed that 90–95% of CD children seem to carry at least a single copy of HLA-DQB1*02, regardless of the remaining HLA-DQ genotype [8]. Moreover, we supported this finding in our monocentric case series, including 269 children with CD, where >97% of all these CD children possessed at least one copy of HLA-DQB1*02 allele in their individual genotype [38]. Here, we looked at the HLA-DQ asset in the FDRs of pediatric CD patients and we found that the almost absolute negative LR was maintained, even when we considered only HLA-DQB1*02 in our analysis.…”

Section: Discussionsupporting

confidence: 85%

Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis

et al. 2019

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Background and Objectives: Celiac disease (CD) is a multifactorial immune-mediated disorder, triggered by the ingestion of gluten in genetically-predisposed subjects carrying MHC-DQ2 and -DQ8 heterodimers, which are encoded by four HLA-DQ allelic variants, overall. This meta-analysis aims at providing further epidemiological support to the predominant relevance of one specific allele, namely HLA-DQB1*02, in the predisposition and genetic risk of CD. Materials and Methods: We performed a search of MEDLINE/PubMed, Embase, Web of Science, and Scopus, retrieving all publications (case–control study, cross-sectional, and retrospective cohort study) on the association between HLA class II polymorphisms and first-degree relatives (FDRs) of children with CD. After a critical reading of the articles, two investigators independently performed data extraction according to the following inclusion criteria: HLA class II genes, any DQ and DR molecules, and CD diagnosed following the current clinical guidelines. A third participant was consulted for discussion to reach an agreement concerning discrepancies. Results: Our search strategy selected 14 studies as being eligible for inclusion, and those were submitted for data extraction and analysis. These studies were published between 1999 and 2016 and, collectively, enrolled 3063 FDRs. Positive and negative likelihood ratios (LR+ and LR−, respectively) for CD diagnosis, according to the presence of the HLA-DQ genotype coding a complete MHC-DQ2 and/or MHC-DQ8 molecules, were 1.449 (CI 1.279–1.642) and 0.187 (CI 0.096–0.362), respectively. If only the isolated presence of HLA-DQB1*02 allele is considered, the pooled estimation of LR+ was 1.659 (CI 1.302–2.155) and, importantly, the LR− still showed a very good discriminatory power of 0.195 (CI 0.068–0.558). Conclusions: Through our differential meta-analysis, comparing the presence of the genotype coding the full MHC-DQ2 and/or DQ8 molecules with the isolated presence of HLA-DQB1*02 allelic variant, we found that the LR− of the latter analysis maintained the same value. This observation, along with previous evidences, might be useful to consider potential cost-effective widened screening strategies for CD in children.

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Section: Discussionsupporting

confidence: 85%

Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis

et al. 2019

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“…Importantly, in addition to the CD screening in patients affected with specific extra-gastrointestinal diseases or manifestations ( 3 , 29 , 30 ), the availability of a cost-effective, but reliable, serological test may be considered for large scale or mass screening, the debate of which is still open ( 5 , 31 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…Celiac disease (CD) is a systemic immune-mediated disorder characterized by a very variable clinical expression, which ranges from classical symptoms of malabsorption to mild gastrointestinal complaints, passing through a multitude of different extra-gastrointestinal manifestations, that can be isolated or combined with the former ( 1 ). Importantly, CD in children can be even asymptomatic and, in these cases, can be investigated only later during adolescence or adulthood, because of some long-term complications, such as growth impairment, pubertal disorders, bone density reduction, fertility issues, occurrence of intestinal malignancy, and/or other autoimmune disorders ( 2 , 3 ). Considering the significant prevalence of CD in children (around or at least 1% of the general population) and its raising incidence ( 4 ), CD should be actively sought, especially in those countries where the dietary regimens have been changing (with an even greater presence of wheat foods) and/or this diagnosis has not been appropriately considered until recent years ( 5 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

Reliability of the Multiplex CytoBead CeliAK Immunoassay to Assess Anti-tTG IgA for Celiac Disease Screening

et al. 2021

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Background and Objective: The diagnosis of Celiac Disease (CD) is first based on the positivity for specific serological markers. The CytoBead CeliAK immunoassay simultaneously measures antibodies (IgA) directed to tissue transglutaminase (tTG), endomysium (EMA), and deamidated gliadin (DG), in addition to providing a control for total IgA levels. The aim of this study is to assess the reliability of this multiplex assay to detect anti-tTG IgA positive patients, compared with a conventional single-parameter enzyme-linked immunosorbent assay (ELISA).Methods: Serum samples from 149 pediatric patients were assessed by both CytoBead CeliAK immunoassay and ELISA, in order to evaluate their concordance for the measurement of anti-tTG IgA.Results: The measurement of anti-tTG IgA by CytoBead CeliAK immunoassay basically showed a complete concordance rate with the conventional and single-parameter ELISA, according to the respective cutoff values (3 U/ml and 10 U/ml).Conclusions: Our comparative analysis demonstrates a substantial equivalency between multiplex CytoBead CeliAK assay and the single-parameter conventional ELISA to assess anti-tTG IgA antibody in the context of the screening for CD in children. Importantly, CytoBead CeliAK assay could present some preanalytic, analytic, and economic advantages.

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“…[16][17] The analysis of other published studies providing precise data about the HLA-DQ genetic background in CD patients could further support this aspect. [18][19][20] Additionally, to further strengthen our thesis, we retrieved two previous HLA studies from Kazakhstan, which actually included much fewer individuals. Kuranov AB et al carried out a study (including 233 Kazakh people) to compare class II HLA alleles between patients with drug resistant tuberculosis (TB, n = 76) and healthy controls (n = 157) in Kazakhstan.…”

Section: Discussionmentioning

confidence: 99%

Genetic predisposition to celiac disease in Kazakhstan: Potential impact on the clinical practice in Central Asia

et al. 2020

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Background Celiac disease (CD) is a systemic immune-mediated disorder developing in HLA genetically predisposed individuals carrying HLA-DQ2 and/or HLA-DQ8 molecules. Recent evidences supported a predominant importance of HLA-DQB1 locus and, in particular, HLA-DQB1*02 alleles. This diagnosis is poorly considered in Kazakhstan, because of the assumption that CD is not prevalent in this population. Objective To demonstrate that the genetic predisposition to CD in Kazakhstan is not negligible and is actually comparable to Western populations. Methods Through the analysis of HLA-DQ genotypes of healthy bone marrow donors from Kazakhstan's national registry, we estimated the HLA-related genetic predisposition to CD in the country. Results We demonstrated that the frequency of CD-related HLA-DQB1 alleles and, as a consequence, of predisposed individuals to CD in Kazakhstan is significant and comparable to countries with the highest disease prevalence. Conclusion Considering the dietary style in Kazakhstan, including wheat as a staple food, these results provided a preliminary background of knowledge to expect a significant CD prevalence in Kazakhstan and Central Asia by implementing appropriate and cost-effective diagnostic strategies.

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HLA‐DQB1*02 allele in children with celiac disease: Potential usefulness for screening strategies

Cited by 13 publications

References 15 publications

Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis

Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis

Reliability of the Multiplex CytoBead CeliAK Immunoassay to Assess Anti-tTG IgA for Celiac Disease Screening

Genetic predisposition to celiac disease in Kazakhstan: Potential impact on the clinical practice in Central Asia

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