Identification of HLA‐DR and ‐DQ alleles conferring susceptibility to pollen allergy and pollen associated food allergy

Boehncke, Wolf‐Henning; Loeliger, Cornelius; Kuehnl, P.; Kalbacher, Hubert; Böhm, Bernhard; Gall, H.

doi:10.1046/j.1365-2222.1998.00246.x

Cited by 35 publications

(25 citation statements)

References 33 publications

(60 reference statements)

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“…HLA has earlier been associated with allergy, playing a role in antigen/allergen presentation 35,36 and IgE dysregulation 37 ; however, the association is not clear and different alleles and allergies have been tested. Few studies have associated HLA DQ2/ DQ8 with allergy.…”

Section: Discussionmentioning

confidence: 99%

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The distribution of HLA DQ2 and DQ8 haplotypes and their association with health indicators in a general Danish population

et al. 2018

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Background: Human leukocyte antigen (HLA) DQ2 and DQ8 are important risk factors for some autoimmune diseases such as celiac disease (CD), but their possible role in other diseases and health conditions is not fully explored. Objectives: The objective of this article is to examine the distribution of HLA DQ2 and HLA DQ8 in an adult general population, and their association with health indicators (diseases, symptoms and biomarkers). Methods: In this cross-sectional, population-based study, 2293 individuals were screened for HLA DQ2 and DQ8; CDassociated alleles (DQA*0201*03*05/DQB*02*0301/0304*0302/0305) and DQB1*02 homozygosity were determined for screen-positive participants. The National Patient Registry provided diagnosis information. Results: A total of 47.7% (1093/2293) individuals were positive for DQ2 and/or DQ8: 31.2% (716/2293) only DQ2, 11.9% (273/ 2293) only DQ8, 4.1% (93/2293) both DQ2 and DQ8. Among nine individuals diagnosed with CD, 89.9% (8/9) had DQ2.5cis, 22.2% (2/9) DQ8 and 22.2% (2/9) DQ2.2 (two both DQ2 and DQ8). HLA DQ2.5 was associated with higher thyroid-stimulating hormone levels, while DQ2/DQ8-positive participants had significantly lower prevalence of irritable bowel syndrome (IBS). DQ2/DQ8 were strongly associated with CD, but no other registry-based diagnoses. Conclusion: In this general Danish population, 47.7% were HLA DQ2/DQ8 positive and thus potentially at risk for CD. All individuals with CD were DQ2/DQ8 positive; the majority DQ2.5. Surprisingly, DQ2/DQ8-positivity was associated with lower IBS prevalence. KeywordsCeliac disease, HLA DQ2, HLA DQ8, epidemiology Received: 29 December 2017; accepted: 21 February 2018 Key summary 1. Summarize the established knowledge on this subject:. Celiac disease is a lifelong autoimmune disease caused by a harmful immune response to gluten proteins in genetically susceptible individuals. . Human leukocyte antigen (HLA) DQ2 and HLA DQ8 are important risk factors for some autoimmune diseases such as celiac disease; however, their possible role in other diseases and health conditions is not fully explored. 2. What are the significant and/or new findings of this study? . Our study showed that 47.7% of individuals were HLA DQ2/DQ8 positive and thus potentially at risk for celiac disease in this general Danish population. . We found that all individuals with celiac disease were HLA DQ2/DQ8 positive; the majority DQ2.5. . Furthermore, HLA DQ2/DQ8 positivity was associated with lower prevalence of irritable bowel syndrome, but not with other diagnoses/diseases.

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Section: Discussionmentioning

confidence: 99%

“…One found an association between DQ8 and hevein-specific IgE immune response in individuals with latex allergy, 38 while others found DQ2 to be associated with olive pollen 39 and the allele DQB1*0301 to be associated with grass pollen allergy. 36 Thus, the association of HLA DQ2/8 with allergy remains unclear.…”

Section: Discussionmentioning

confidence: 99%

The distribution of HLA DQ2 and DQ8 haplotypes and their association with health indicators in a general Danish population

et al. 2018

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“…In the early 1980s, Marsh et al [2] observed an association between an MHC-II-encoding HLA genotype and the immune response to the short ragweed pollen allergen Amb a 5 (Ra5). Since then, several HLA genotypes have been shown to be associated with respiratory and food allergies [3,4,5,6]. The correlation between an HLA genotype and sensitization to an allergen is strongest if the allergen contains a single immunodominant T cell epitope, as shown for the major mugwort pollen allergen Art v 1 [7].…”

Section: Introductionmentioning

confidence: 99%

Role of Human Leucocyte Antigen DQ in the Presentation of T Cell Epitopes in the Major Cow’s Milk Allergen αs1-Casein

Ruiter

Rozemuller²,

Dijk³

et al. 2007

Int Arch Allergy Immunol

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Background: Little is known about the association between human leucocyte antigen (HLA) and cow’s milk allergy (CMA). The aim of the present study was to determine the HLA restriction of T cell clones (TCCs) specific to αs1-casein, the most abundant milk protein, and to study possible HLA class II allele associations with CMA. Methods: αs1-Casein-specific TCCs were derived from 6 children with CMA, 9 atopic children without CMA and 5 non-atopic children. T cell epitope specificity was defined by stimulation with overlapping peptides, spanning the αs1-casein molecule. HLA restriction was determined in proliferation assays using antibodies blocking either HLA-DP, HLA-DQ or HLA-DR. HLA genotyping was performed in 32 subjects with CMA, 23 atopic and 22 non-atopic individuals. Results: Ten TCCs were restricted to HLA-DQ, 6 TCCs to HLA-DR and 4 TCCs to HLA-DP. The sequence in αs1-casein that was most immunogenic to T cells from children with CMA contained T cell epitopes restricted to DQB1*0201, DPB1*0401 and DRB1*1501. The DQB1*0501 allele frequency was lower in children with CMA than in non-atopic children, but this difference could not be confirmed in an additional group of subjects with and without CMA. Conclusions: HLA-DQ plays a substantial role in the presentation of T cell epitopes in αs1-casein. However, HLA class II allele frequencies do not show major differences between cow’s milk allergic, atopic and non-atopic subjects. T cell epitopes in the most immunogenic region are presented by various abundantly present HLA genotypes. Therefore, this sequence may be a suitable target for peptide immunotherapy.

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“…Examples are an association of HLA-DQ7 with cows' milk protein allergy in Italian children (Camponeschi et al, 1997), HLA-DRB1, DQB1, and DPB1 with peanut allergy (Howell et al, 1998), and HLA-DRB1*08 for peanut allergy (six-fold increased risk) and HLA-DRB1*12 (13-fold increased risk) for carrot allergy (Boehncke et al, 1998). Sénéchal et al (1999) described involvement of HLA-DR7 in the allergic response to apple and pollen, but concluded that the increased susceptibility conferred by HLA-DR7 was more related to atopy than to allergen-specific responses.…”

Section: Genetic Factors -Specific Immune-response Genesmentioning

confidence: 99%

Opinion of the Scientific Panel on Dietetic products, nutrition and allergies [NDA] on a request from the Commission relating to the evaluation of allergenic foods for labelling purposes

2004

EFS2

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Identification of HLA‐DR and ‐DQ alleles conferring susceptibility to pollen allergy and pollen associated food allergy

Cited by 35 publications

References 33 publications

The distribution of HLA DQ2 and DQ8 haplotypes and their association with health indicators in a general Danish population

The distribution of HLA DQ2 and DQ8 haplotypes and their association with health indicators in a general Danish population

Role of Human Leucocyte Antigen DQ in the Presentation of T Cell Epitopes in the Major Cow’s Milk Allergen αs1-Casein

Opinion of the Scientific Panel on Dietetic products, nutrition and allergies [NDA] on a request from the Commission relating to the evaluation of allergenic foods for labelling purposes

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