Phenotypic variance in childhood coeliac disease and the HLA-DQ/DR dose effect

Vermeulen, Beatrijs A. N.; Esch, Caroline E. Hogen; Yüksel, Zehre; Koning, Frits; Verduijn, Willem; Doxiadis, Ilias I.N.; Schreuder, G. M. T.; Mearin, M. L.

doi:10.1080/00365520802116422

Cited by 24 publications

(27 citation statements)

References 34 publications

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“…As expected the HLA-DQ2 homozygous status, or anyway associated with a b2 chain double dose (DQ2,B1*02/*02), leads to the highest risk to develop CD which in our study was 1:7 vs. 1:47 in DQ2 heterozygous subjects. These data are concordant with what is affirmed by many authors (3,12,(19)(20)(21), while Megiorni et al (10) found the highest risk value for DQ2 and DQ8 positive subjects. In our experience these individuals are comprised in an intermediate risk category (1:41).…”

Section: Discussionsupporting

confidence: 82%

“…We showed how the presence of DQB1*02 allele (b2 chain) in DQ8 positive individuals increases the risk of developing CD twofold (from 1:85 to 1:43). DQB1*02 heterozygous subjects (b2, B1*02/X) are comprised in a low risk category (1:75), together with subjects DQ8 positive when DQB1*02 and DQB1*0302 negative (1:85), in line with what was observed by other authors (3,19) and in contrast with Megiorni et al (10) who found a risk lower for b2 heterozygous subjects than in the general population. Values lower than the disease prevalence in the general population were demonstrated for a5 subjects (1: 1818) or DQ2, DQ8, b2, a5 negative subjects (1:3580).…”

Section: Discussioncontrasting

confidence: 54%

“…HLA related genes are responsible for 40% of the genetic contribution in CD (2) and about 30% of the general population shows the HLA-DQ2 and/or DQ8 haplotype although only 1% develops CD; this means that HLA-DQ2 and HLA-DQ8 are necessary but not sufficient factors to cause CD. The absence of these alleles is significant for high negative predictive value; in fact, virtually all CD patients carry HLA-DQ2 and/ -DQ8 molecules or one chain of the DQ2 heterodimer (3)(4)(5). Although CD is one of the most common chronic disease in western countries, most affected individuals go undiagnosed because of atypical symptoms or absence of symptoms (6,7).…”

Section: Introductionmentioning

confidence: 99%

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HLA-DQ typing in the diagnostic algorithm of celiac disease

Piccini

Vascotto

Serracca

et al. 2012

Rev. esp. enferm. dig.

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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.

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Section: Discussionsupporting

confidence: 82%

Section: Discussioncontrasting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

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HLA-DQ typing in the diagnostic algorithm of celiac disease

Piccini

Vascotto

Serracca

et al. 2012

Rev. esp. enferm. dig.

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“…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.…”

Section: Discussionsupporting

confidence: 57%

“…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).…”

Section: Discussionmentioning

confidence: 67%

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

Fernández-Cavada-Pollo¹,

Alcalá-Peña²,

Vargas-Pérez³

et al. 2013

Rev. esp. enferm. dig.

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Clinical practice

Kneepkens

Blomberg

2012

Eur J Pediatr

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Coeliac disease (CD) is an immune-mediated systemic condition elicited by gluten and related prolamines in genetically predisposed individuals and characterised by gluten-induced symptoms and signs, specific antibodies, a specific human leukocyte antigen (HLA) type and enteropathy. The risk of coeliac disease is increased in first-degree relatives, certain syndromes including Down syndrome and autoimmune disorders. It is thought to occur in 1 in 100–200 individuals, but still only one in four cases is diagnosed. Small-bowel biopsy is no longer deemed necessary in a subgroup of patients, i.e. when all of the following are present: typical symptoms or signs, high titres of and transglutaminase antibodies, endomysial antibodies, and HLA-type DQ2 or DQ8. In all other cases, small-bowel biopsy remains mandatory for a correct diagnosis. Therapy consists of a strictly gluten-free diet. This should result in complete disappearance of symptoms and of serological markers. Adequate follow-up is considered essential. Conclusion: Although small-bowel biopsy may be omitted in a minority of patients, small-bowel biopsy is essential for a correct diagnosis of CD in all other cases. Diagnostic work-up should be completed before treatment with gluten-free diet instituted.

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Phenotypic variance in childhood coeliac disease and the HLA-DQ/DR dose effect

Abstract: No correlation was found between disease severity and a double HLA-DQ2 gene dose.

Cited by 24 publications

References 34 publications

HLA-DQ typing in the diagnostic algorithm of celiac disease

HLA-DQ typing in the diagnostic algorithm of celiac disease

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

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