Characteristics of childhood peanut allergy in the Australian Capital Territory, 1995 to 2007

Mullins, Raymond J; Dear, Keith; Tang, Mimi L.K.

doi:10.1016/j.jaci.2008.12.1116

Cited by 103 publications

(72 citation statements)

References 23 publications

(19 reference statements)

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“…Peanut allergy persists as one of the major contributors to anaphylactic deaths caused by food ingestion [28], and with increased incidence within Westernised societies [29,30,31,32,33] and limited treatment options, the development of novel therapeutic intervention is dependant on further improving the understanding of the mechanism of this disease at an intrinsic level.…”

Section: Discussionmentioning

confidence: 99%

Peanut Allergens Alter Intestinal Barrier Permeability and Tight Junction Localisation in Caco-2 Cell Cultures¹

Price

Ackland²,

Burks³

et al. 2014

Cell Physiol Biochem

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Background/Aims: Allergen absorption by epithelia may play an important role in downstream immune responses. Transport mechanisms that can bypass Peyer's patches include transcellular and paracellular transport. The capacity of an allergen to cross via these means can modulate downstream processing of the allergen by the immune system. The aim of this study was to investigate allergen-epithelial interactions of peanut allergens with the human intestinal epithelium. Methods: We achieved this using the human Caco-2 cell culture model, exposed to crude peanut extract. Western and immunofluorescence analysis were used to identify the cellular and molecular changes of peanut extract on the intestinal epithelium. Results: Following exposure of Caco-2 cells to peanut extract, binding of the peanut allergens Ara h 1 and Ara h 2 to the apical cellular membrane and transcytosis across the monolayers were observed. Additionally, the co-localisation of the transmembrane tight junction proteins occludin, JAM-A and claudin-1, with the intracellular adhesion protein ZO-1 was modified. Conclusion: Disruption of Caco-2 barrier integrity through tight junction disruption may enable movement of peanut proteins across the intestinal epithelium. This accounts for peanut's increased allergenicity, compared to other food allergens, and provides an explanation for the potency of peanut allergens in immune response elicitation.

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Section: Discussionmentioning

confidence: 99%

Peanut Allergens Alter Intestinal Barrier Permeability and Tight Junction Localisation in Caco-2 Cell Cultures¹

Price

Ackland²,

Burks³

et al. 2014

Cell Physiol Biochem

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“…The prevalence of food allergy has continued to increase over the past few decades [1,2,3,4,5]. The reason for the increasing prevalence of sensitivity to certain foods, and the nature of the allergen-epithelial interactions, remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Identifying Epithelial Endocytotic Mechanisms of the Peanut Allergens Ara h 1 and Ara h 2

Price

Ackland²,

Suphioglu³

2017

Int Arch Allergy Immunol

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Background: Peanuts are still one of the highest contributors to anaphylactic deaths after ingestion of a food allergen. At the molecular level, interactions between peanut allergens and the intestinal epithelium are largely unexplored. Previous findings by our research group demonstrated that the major peanut allergens, i.e., Ara h 1, Ara h 2, Ara h 3, and Ara h 6, were able to cross the Caco-2 human cell culture model of the intestinal epithelium. This research broadened our investigation to identify the mechanisms by which the Caco-2 monolayers uptake peanut allergens, specifically by endocytosis. Here, we aim to increase our understanding of allergen-epithelial interactions and, more broadly, the pathway from allergen to allergy. Methods: The human Caco-2 cell culture model was exposed to peanut extract and a combination of confocal microscopy and inhibition studies were used to identify the endocytotic mechanisms of peanut allergens in intestinal epithelia. Results: Our findings demonstrate that the peanut allergens Ara h 1 and Ara h 2 are transported through intestinal epithelia initially via early endosomes using multiple endocytotic mechanisms. From there, they are then transported to late endosomes and ultimately to lysosomes. Conclusions: These novel findings provide insight into the allergen-epithelial interactions of peanut allergens with the intestinal epithelium. Consequently, this opens the possibility of the use of these endocytotic pathways as targets for inhibitors in therapeutic development and preventative measures for peanut allergy in the future.

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“…Despite recent increases in anaphylaxis-related emergency department visits and hospital admissions in the United Kingdom [36], Australia [37], and United States [38]; more frequent anaphylaxis diagnoses in community-based studies [39,40]; and specific evidence of increased peanut allergy prevalence in birth cohort and community-based studies [41][42][43], risk factors for food allergy and anaphylaxis remain poorly defined. Hypotheses for these increases include changes in exposure to microbial products, topical sensitization, Caesarean section births, antacid medication use by infants, food processing methods, timing of introduction of allergenic food, or factors related to socioeconomic status or location of residence, as recently reviewed [5,[44][45][46][47].…”

Section: Childhood Food Allergymentioning

confidence: 99%

Latitude, Sunlight, Vitamin D, and Childhood Food Allergy/Anaphylaxis

Mullins

Camargo

2011

Curr Allergy Asthma Rep

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Vitamin D is widely known for its role in bone metabolism, but this sterol hormone also has important immunomodulatory properties. Vitamin D is produced by the conversion of D3 in the skin following UVB exposure, or after ingestion of D2 or D3. At the extremes of latitude, there is insufficient UVB intensity in the autumn and winter months for adequate synthesis of vitamin D to occur. Growing evidence implicates vitamin D deficiency in early life in the pathogenesis of nonskeletal disorders (e. g., type 1 diabetes and multiple sclerosis) and, more recently, atopic disorders. Several studies have reported higher rates of food allergy/anaphylaxis or proxy measures at higher absolute latitudes. Although causality remains to be determined, these studies suggest a possible role for sunlight and/or vitamin D in the pathogenesis of food allergy/anaphylaxis.

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Characteristics of childhood peanut allergy in the Australian Capital Territory, 1995 to 2007

Abstract: Although most characteristics of peanut allergy have changed little over the period of the last 13 years (onset age, sex, comorbidity, severity), later onset was associated with greater risk of anaphylaxis. Our data are consistent with a rise in incidence.

Cited by 103 publications

References 23 publications

Peanut Allergens Alter Intestinal Barrier Permeability and Tight Junction Localisation in Caco-2 Cell Cultures¹

Peanut Allergens Alter Intestinal Barrier Permeability and Tight Junction Localisation in Caco-2 Cell Cultures¹

Identifying Epithelial Endocytotic Mechanisms of the Peanut Allergens Ara h 1 and Ara h 2

Latitude, Sunlight, Vitamin D, and Childhood Food Allergy/Anaphylaxis

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Characteristics of childhood peanut allergy in the Australian Capital Territory, 1995 to 2007

Abstract: Although most characteristics of peanut allergy have changed little over the period of the last 13 years (onset age, sex, comorbidity, severity), later onset was associated with greater risk of anaphylaxis. Our data are consistent with a rise in incidence.

Cited by 103 publications

References 23 publications

Peanut Allergens Alter Intestinal Barrier Permeability and Tight Junction Localisation in Caco-2 Cell Cultures1

Peanut Allergens Alter Intestinal Barrier Permeability and Tight Junction Localisation in Caco-2 Cell Cultures1

Identifying Epithelial Endocytotic Mechanisms of the Peanut Allergens Ara h 1 and Ara h 2

Latitude, Sunlight, Vitamin D, and Childhood Food Allergy/Anaphylaxis

Contact Info

Product

Resources

About

Peanut Allergens Alter Intestinal Barrier Permeability and Tight Junction Localisation in Caco-2 Cell Cultures¹

Peanut Allergens Alter Intestinal Barrier Permeability and Tight Junction Localisation in Caco-2 Cell Cultures¹