Loss‐of‐function mutations in the gene encoding filaggrin underlie a Japanese family with food‐dependent exercise‐induced anaphylaxis

Mizuno, Osamu; Nomura, Toshifumi; Ohguchi, Yuka; Suzuki, Shotaro; Nomura, Yukiko; Hamade, Yohei; Hoshina, Daichi; Sandilands, Aileen; Akiyama, Masashi; McLean, William; Abe, Riichiro; Shimizu, Hiroshi

doi:10.1111/jdv.12441

Cited by 12 publications

(9 citation statements)

References 13 publications

(22 reference statements)

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“…To the best of our knowledge, there have been only a few reports describing clinical features of patients with compound heterozygous FLG mutations . Our present results suggest that patients with bi‐allelic FLG mutations do not always have severe AD.…”

Section: Discussionsupporting

confidence: 49%

Compound heterozygotes for filaggrin gene mutations do not always show severe atopic dermatitis

Sekiya

Kono

Tsujiuchi

et al. 2016

Acad Dermatol Venereol

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Section: Discussionsupporting

confidence: 49%

Compound heterozygotes for filaggrin gene mutations do not always show severe atopic dermatitis

Sekiya

Kono

Tsujiuchi

et al. 2016

Acad Dermatol Venereol

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“…There is increasing evidence that an epidermal barrier defect may play an important role. Loss-offunction mutations in the gene encoding filaggrin, a key epidermal protein in skin barrier function, are known to be significant predisposing factors for the development of atopic diseases such as eczema, asthma, and rhinitis [69] and might also be involved in the pathogenesis of WDEIA [70].…”

Section: Pathomechanismmentioning

confidence: 99%

Wheat‐dependent exercise‐induced anaphylaxis

Scherf

Brockow

Biedermann

et al. 2015

Clin Experimental Allergy

156

131

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Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a rare, but potentially severe food allergy exclusively occurring when wheat ingestion is accompanied by augmenting cofactors. It is clinically characterized by anaphylactic reactions ranging from urticaria and angioedema to dyspnoea, hypotension, collapse, and shock. WDEIA usually develops after ingestion of wheat products followed by physical exercise. Other cofactors are acetylsalicylic acid and other non-steroidal anti-inflammatory drugs, alcohol, and infections. The precise mechanisms of WDEIA remain unclear; exercise and other cofactors might increase gastrointestinal allergen permeability and osmolality, redistribute blood flow, or lower the threshold for IgE-mediated mast cell degranulation. Among wheat proteins, ω5-gliadin and high-molecular-weight glutenin subunits have been reported to be the major allergens. In some patients, WDEIA has been discussed to be caused by epicutaneous sensitization with hydrolysed wheat gluten included in cosmetics. Diagnosis is made based on the patient's history in combination with allergy skin testing, determination of wheat-specific IgE serum antibodies, basophil activation test, histamine release test, and/or exercise challenge test. Acute treatment includes application of adrenaline or antihistamines. The most reliable prophylaxis of WDEIA is a gluten-free diet. In less severe cases, a strict limitation of wheat ingestion before exercise and avoidance of other cofactors may be sufficient.

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“…There are two contradicting reports showing wheat-dependent exercise-induced anaphylaxis (WDEIA) in a patient without filaggrin mutation and an association of mutation in the filaggrin gene with WDIEA in a Japanese family [65,66]. The available evidence showed that C3H/Hej and Balb/c mice strains have different susceptibilities to gliadin-induced allergy, suggesting genetic control of the disease [30].…”

Section: Insights In To the Molecular Mechanisms Of Wheat Allergenmentioning

confidence: 99%

Advances in Molecular Mechanisms of Wheat Allergenicity in Animal Models: A Comprehensive Review

Jin

Acharya

et al. 2019

Molecules

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The prevalence of wheat allergy has reached significant levels in many countries. Therefore, wheat is a major global food safety and public health issue. Animal models serve as critical tools to advance the understanding of the mechanisms of wheat allergenicity to develop preventive and control methods. A comprehensive review on the molecular mechanisms of wheat allergenicity using animal models is unavailable at present. There were two major objectives of this study: To identify the lessons that animal models have taught us regarding the molecular mechanisms of wheat allergenicity and to identify the strengths, challenges, and future prospects of animal models in basic and applied wheat allergy research. Using the PubMed and Google Scholar databases, we retrieved and critically analyzed the relevant articles and excluded celiac disease and non-celiac gluten sensitivity. Our analysis shows that animal models can provide insight into the IgE epitope structure of wheat allergens, effects of detergents and other chemicals on wheat allergenicity, and the role of genetics, microbiome, and food processing in wheat allergy. Although animal models have inherent limitations, they are critical to advance knowledge on the molecular mechanisms of wheat allergenicity. They can also serve as highly useful pre-clinical testing tools to develop safer genetically modified wheat, hypoallergenic wheat products, novel pharmaceuticals, and vaccines.

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Loss‐of‐function mutations in the gene encoding filaggrin underlie a Japanese family with food‐dependent exercise‐induced anaphylaxis

Abstract: These results indicate that FLG mutations might be involved in the pathogenesis of WDEIA in the present case.

Cited by 12 publications

References 13 publications

Compound heterozygotes for filaggrin gene mutations do not always show severe atopic dermatitis

Compound heterozygotes for filaggrin gene mutations do not always show severe atopic dermatitis

Wheat‐dependent exercise‐induced anaphylaxis

Advances in Molecular Mechanisms of Wheat Allergenicity in Animal Models: A Comprehensive Review

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