DNA damage signaling and polyploid macrophages in chronic inflammation

Veronika Horn | Antigoni Triantafyllopoulou

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Food Allergy: Update on Prevention and Tolerance

Publication date: Available online 27 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): George Du Toit, Hugh Sampson, Marshall Plaut, Wesley Burks, Cezmi Akdis, Gideon Lack
Of the many possible hypotheses which explain the recent rise in childhood food allergy, the dual allergen exposure hypothesis has been the most extensively investigated. This chapter serves as a review and update on the prevention of food allergy, and focuses on recently published Randomized Controlled Trials (RCTs) exploring the efficacy of oral tolerance induction in infancy for the prevention of food allergy. As a result of these RCTs, National Institutes of Health (NIH) recommendations now actively encourage the early introduction of peanut for the prevention of peanut allergy and other countries/settings recommend the inclusion of potential common food allergens including peanut and egg in complementary feeding regimens commencing at approximately 6 months of age, but not before 4 months.^1-3 Further studies which explore the efficacy of oral tolerance induction to other common food allergens, and which focus on optimal timing, duration and adherence are required.



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Dual loss of p110δ PI3-kinase and SKAP (KNSTRN) expression leads to combined immunodeficiency and multisystem syndromic features

Publication date: Available online 26 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Nigel Sharfe, Ariana Karanxha, Harjit Dadi, Daniele Merico, David Chitayat, Jo-Anne Herbrick, Spencer Freeman, Sergio Grinstein, Chaim M Roifman
BackgroundWe previously reported a novel syndrome characterized by combined immunodeficiency associated with severe developmental defects - subsequently known as Roifman-Chitayat Syndrome (RCS; OMIM 613328). Linkage analysis identified two disease-associated loci.ObjectiveTo identify the genetic defect in these patients and characterize their immunological cellular abnormalities.MethodsGenetic, immunological, protein and cellular functional analyses were used to identify and characterize patient genetic deficiencies and aberrant patient cell behaviour.ResultsDeleterious variants were found at both loci identified by linkage analysis: a homozygous stop codon in PI3-kinase p110δ (PIK3CD) and a homozygous frame shift mutation in SKAP (KNSTRN), both ablating protein expression. RCS patients display aberrant B cell development, similar to p110δ deficient mice, but also aberrant T cell spreading, cell-cell interaction and migration. Patients also display significant developmental abnormalities not seen in p110δ knockouts (e.g. optic nerve atrophy, skeletal anomalies) that we ascribe to loss of SKAP. Aberrant SKAP expression can prolong anaphase and this may contribute to developmental defects. However, we also identified MAP4 microtubule-binding protein as a novel SKAP-binding partner and show it undergoes re-localization in patient T cells, with associated areas of aberrant microtubule hyper-stabilization, likely contributing not only to the altered properties of RCS lymphoid cells but also developmental defects.ConclusionsThe complex Roifman-Chitayat Syndrome presentation, with combined developmental and immunological defects, is associated with a combined deficiency of two genes products, PI3-kinase p110δ and SKAP, both of which appear to play a significant role in the disease.

Teaser

Patients with Roifman-Chitayat syndrome suffer repeated infections due to combined immunodeficiency and display a wide array of syndromic features encompassing developmental delay, optic nerve atrophy and skeletal anomalies. We show here for the first time that complete SKAP and PI3K p110δ deficiencies lead to this complex syndrome.


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Self-reported adverse food reactions and anaphylaxis in the SchoolNuts study: A population-based study of adolescents

Publication date: Available online 23 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Vicki L. McWilliam, Jennifer J. Koplin, Michael J. Field, Mari Sasaki, Shyamali C. Dharmage, Mimi L.K. Tang, Susan M. Sawyer, Rachel L. Peters, Katrina J. Allen
BackgroundAdolescents are at the highest risk of death from anaphylaxis, yet few population-based studies have described the frequencies and risk factors for allergic reactions caused by accidental allergen ingestion in this group.MethodsWe describe the prevalence, frequency, and associated risk factors for recent adverse food reactions in 10- to 14-year-olds in Melbourne, Australia, recruited from a stratified, random, population-based sample of schools (SchoolNuts, n = 9663; 48% response rate). Self-reported food allergy and adverse reaction details, including anaphylaxis, were identified by using a student questionnaire over the past year.ResultsOf 547 students with possible IgE-mediated food allergy, 243 (44.4%; 95% CI, 40.3% to 48.7%) reported a reaction to a food. Fifty-three (9.7%; 95% CI, 7.2% to 12.2%) students reported 93 anaphylaxis episodes. Peanut and tree nuts were the most common food triggers. Among students with current IgE-mediated food allergy, those with resolved or current asthma (adjusted odds ratio [aOR], 1.9 [95% CI, 1.1-1.3] and 1.7 [95% CI, 1.1-2.6]) and those with more than 2 food allergies (aOR, 1.9 [95% CI, 1.1-3.1]) were at greatest risk of any adverse food reaction, and those with nut allergy were most at risk of severe reactions (aOR, 2.9 [95% CI, 1.1-4.4]). Resolved or current asthma was not associated with increased risk of severe reactions (aOR, 0.8 [95% CI, 0.3-2.2] and 1.6 [95% CI, 0.7-3.7]).ConclusionsAdolescents with food allergy are frequently exposed to food allergens. Those with asthma and more than 2 food allergies were at the greatest risk for adverse food reactions. Those with nut allergies were most at risk of severe reactions.



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Food Allergy in the developing world

Publication date: Available online 22 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Agnes SY. Leung, Gary WK. Wong, Mimi LK. Tang




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Food Allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention and management

Publication date: Available online 21 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Scott H. Sicherer, Hugh A. Sampson
This review provides general information to serve as a primer for those embarking on understanding food allergy and also details advances and updates in epidemiology, pathogenesis, diagnosis and treatment that have occurred over the four years since our last comprehensive review. Although firm prevalence data are lacking, there is a strong impression that food allergy has increased, and rates as high as ∼10% have been documented. Genetic, epigenetic and environmental risk factors are being increasingly elucidated, opening the potential for improved prevention and treatment strategies targeted to those at risk. Insights on pathophysiology are revealing a complex interplay of epithelial barrier, mucosal and systemic immune response, route of exposure and microbiome among other influences resulting in allergy or tolerance. The diagnosis of food allergy is largely reliant on the medical history, tests for sensitization, and oral food challenges, but emerging use of component resolved diagnostics are improving diagnostic accuracy. Additional novel diagnostics such as basophil activation tests, determination of epitope binding, DNA methylation signatures and bioinformatics approaches will further change the landscape. A number of prevention strategies are under investigation, but early introduction of peanut has been advised as a public health measure based on existing data. Management remains largely based on allergen avoidance, but a panoply of promising treatment strategies are in phase 2 and 3 studies, giving immense hope that better treatment will be imminently and widely available, while numerous additional promising treatments are in the preclinical and clinical pipeline.



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Bedroom allergen exposures in US households

Publication date: Available online 30 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Päivi M. Salo, Jesse Wilkerson, Kathryn M. Rose, Richard D. Cohn, Agustin Calatroni, Herman E. Mitchell, Michelle L. Sever, Peter J. Gergen, Peter S. Thorne, Darryl C. Zeldin
BackgroundBedroom allergen exposures contribute to allergic disease morbidity because people spend considerable time in bedrooms, where they come into close contact with allergen reservoirs.ObjectiveWe investigated participant and housing characteristics, including sociodemographic, regional, and climatic factors, associated with bedroom allergen exposures in a nationally representative sample of the US population.MethodsData were obtained from National Health and Nutrition Examination Survey 2005-2006. Information on participant and housing characteristics was collected by using questionnaires and environmental assessments. Concentrations of 8 indoor allergens (Alt a 1, Bla g 1, Can f 1, Fel d 1, Der f 1, Der p 1, Mus m 1, and Rat n 1) in dust vacuumed from nearly 7000 bedrooms were measured by using immunoassays. Exposure levels were classified as increased based on percentile (75th/90th) cutoffs. We estimated the burden of exposure to multiple allergens and used multivariable logistic regression to identify independent predictors for each allergen and household allergen burden.ResultsAlmost all participants (>99%) had at least 1 and 74.2% had 3 to 6 allergens detected. More than two thirds of participants (72.9%) had at least 1 allergen and 18.2% had 3 or more allergens exceeding increased levels. Although exposure variability showed significant racial/ethnic and regional differences, high exposure burden to multiple allergens was most consistently associated with the presence of pets and pests, living in mobile homes/trailers and older and rental homes, and living in nonmetropolitan areas.ConclusionsExposure to multiple allergens is common. Despite highly variable exposures, bedroom allergen burden is strongly associated with the presence of pets and pests.

Graphical abstract

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