HLA Polymorphisms and Food Allergy Predisposition

Kostara, Maria; Chondrou, Vasiliki; Sgourou, Argyro; Douros, Konstantinos; Tsabouri, Sophia

doi:10.1055/s-0040-1708521

Cited by 14 publications

(14 citation statements)

References 37 publications

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“…HLA‐DRB1 and HLA‐DQB1 (encoding for the β‐chains) belong to MHC class II, are closely linked within the genetic loci, share common regulatory features in their promoter regions 25 and common CpG islands within exon 2 18 . Also, genetic variants within HLA‐DQB1 and HLA‐DRB1 sequences have strongly been associated with predisposition to FA, 15,16 but the linkage between DNA methylation and SNPs across these loci has not yet been elucidated. CpG73 and CpG41 also include DNAse hypersensitive sites, indicating essential trans‐acting factor occupancy.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic/genetic variations in CG‐rich elements of immune‐related genes contribute to food allergy development during childhood

Kostara

Chondrou

Fotopoulos

et al. 2022

Pediatric Allergy Immunology

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Background Genetic areas of FOXP3 TSDR, human leukocyte antigen‐G (HLA‐G) upstream of CpG island 96, CpG41 and CpG73 islands of the HLA‐DRB1 and HLA‐DQB1 genes respectively, previously documented to display immune‐modulatory properties, were subjected to epigenetic/genetic analysis to assess their influence in IgE‐mediated food allergy (FA) development in children. Methods Sixty‐four orally challenged and IgE‐tested food allergic subjects together with 44 controls were recruited. Targeted pyrosequencing analysis to detect DNA methylation status and genetic variations was utilized and experimental results obtained were analyzed by a statistical software platform and correlated to clinical data. Also, transcription factor (TF) binding sites in study areas were unmasked by the JASPAR prediction database. Results Parents’ smoking was significantly correlated with aberrant methylation patterns, regardless of food allergic or control status. HLA‐G promoter region showed a trend for hypomethylation in food allergic subjects, with one of the CG sites displaying significantly decreased methylation values. Rs1233333, residing within the HLA‐G promoter region preserved a protective role toward DNA methylation. Variable methylation patterns were recorded for CpG41 of the HLA‐DRB1 gene and hypermethylation of the region was significantly correlated with the presence of single nucleotide polymorphisms (SNPs). TFs’ recognition sites, located in studied genetic areas and exerting pivotal regulatory biological roles, are potentially affected by divergent DNA methylation status. Conclusions We propose that HLA‐G expression is triggered by food‐derived allergens, providing a TregFoxP3‐/HLA‐G+ subpopulation generation to promote direct immune tolerance. Furthermore, clear evidence is provided for the underlying co‐operation of genetic polymorphisms with epigenetic events, mainly at the CpG41 island of the HLA‐DRB1 gene, which needs an extended investigation and elucidation.

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Section: Resultsmentioning

confidence: 99%

Epigenetic/genetic variations in CG‐rich elements of immune‐related genes contribute to food allergy development during childhood

Kostara

Chondrou

Fotopoulos

et al. 2022

Pediatric Allergy Immunology

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“…Associations between CR sensitization and HLA class II antigens have been suggested 56,57 and consistently shown in food allergies. 58,59 In addition, we measured basal levels of non-antigen specific regulatory T cells and observed that T cells inversely correlated with the effector CD4+ T cell responses although it did not reach statistical significance. These results were not unexpected and were consistent with previous observations from Bacher et al 30 .…”

Section: Discussionmentioning

confidence: 99%

“…Associations between CR sensitization and HLA class II antigens have been suggested 56 , 57 and consistently shown in food allergies. 58 , 59 …”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen‐specific T cell responses in allergic sensitized children

Antunes

Sutherland

Schulten

et al. 2021

Clinical & Translational All

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Background Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen‐specific T cell reactivity in a cohort of CR allergic children with asthma. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild‐to‐moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. Results Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL‐4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. Conclusions Our results demonstrate that in children with mild‐to‐moderate asthma, CR‐specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.

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“…HLA-DRB1 and HLA-DQB1 (encoding for the β-chains) belong to MHC class II, are closely linked within the genetic loci, share common regulatory features in their promoter regions 23 and common CpG islands within exon 2 18 . Also, genetic variants within HLA-DQB1 and HLA-DRB1 sequences have strongly been associated with predisposition to FA 15,16 , but the linkage between DNA methylation and single-nucleotide polymorphisms (SNPs) across these loci has not yet been elucidated. CpG73 and CpG41 also include DNAse hypersensitive sites, indicating essential trans-acting factor occupancy.…”

Section: Methylation Status Of Hla-drb1 Cpg41 and Co-existence Of Gen...mentioning

confidence: 99%

“…Cell-processed antigens' presentation by MHC class II to CD4 + T lymphocytes, stimulates the antigen-specific hypersensitivity type I allergic reaction. GWAS studies and review analysis have provided convincing evidence that HLA-DRand HLA-DQ genes' polymorphic regions harbor significant genetic and epigenetic risk for FA 15,16 .…”

Section: Introductionmentioning

confidence: 99%

Epigenetic/Genetic variations in CG-rich elements of immune-related genes contribute to food allergy development during childhood

Kostara

Chondrou

Fotopoulos

et al. 2022

Preprint

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Background: Genetic areas of FOXP3 TSDR, HLA-G upstream of CpG island 96, CpG41 and CpG73 islands of the HLA‐DRB1 and HLA-DQB1 genes respectively, previously documented to display immune modulatory properties, were subjected to epigenetic/genetic analysis to assess their influence in IgE-mediated food allergy (FA) development in children. Methods: 64 orally challenged and IgE- tested food allergic subjects together with 44 controls were recruited. Targeted pyrosequencing analysis, to detect DNA methylation status and genetic variations was utilized and experimental results obtained were analysed by statistical software platform and correlated to clinical data. Also, transcription factor (TF) binding sites at study areas were unmasked by the JASPAR prediction database. Results: Parents’ smoking was significantly correlated with aberrant methylation patterns, regardless food allergic or control status. HLA-G promoter region showed a trend for hypomethylation in food allergic subjects, with one of the CG sites displaying significantly decreased methylation values. Rs1233333, residing within HLA-G promoter region preserved a protective role towards DNA methylation. Variable methylation patterns were recorded for CpG41 of the HLA‐DRB1 gene and hypermethylation of the region was significantly correlated with the presence of (Single Nucleotide Polymorphisms) SNPs. TFs’ recognition sites, located at studied genetic areas and exerting pivotal regulatory biological roles, are potentially affected from divergent DNA methylation status. Conclusions: We propose that HLA-G expression is triggered by food derived allergens, providing a TregFoxP3-/HLA-G+ subpopulation generation and direct immune-tolerance. Furthermore, clear evidence is provided for the underlying co-operation of genetic polymorphisms with epigenetic events, mainly at CpG41 island of HLA-DRB1 gene, which need an extended investigation and elucidation.

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HLA Polymorphisms and Food Allergy Predisposition

Cited by 14 publications

References 37 publications

Epigenetic/genetic variations in CG‐rich elements of immune‐related genes contribute to food allergy development during childhood

Epigenetic/genetic variations in CG‐rich elements of immune‐related genes contribute to food allergy development during childhood

Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen‐specific T cell responses in allergic sensitized children

Epigenetic/Genetic variations in CG-rich elements of immune-related genes contribute to food allergy development during childhood

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