Nicolette W. de Jong

Prevalence of sensitization to the predatory mite Amblyseius cucumeris as a new occupational allergen in horticulture

Background: Protection against thrips, a common pest in bell pepper horticulture is effectively possible without pesticides by using the commercially available predatory mite Amblyzeius cucumeris (Ac). The prevalence of sensitization to Ac among exposed greenhouse employees and its clinical relevance was studied.

Prevalence of natural rubber latex allergy (Type I and Type IV) in laboratory workers in The Netherlands

The objective of the study was to study the prevalence of Type IV and Type I allergy to natural rubber latex (NRL) in a population at risk in the Netherlands. Laboratory workers regularly using gloves were invited to complete a questionnaire and to be tested. We performed patch tests with standard contact allergens, rubber additives, glove powder and pieces of 4 gloves; prick tests with inhalant allergens, glove extracts, glove powder and fruit extracts; and RASTs. Glove‐related hand dermatitis was reported in 36.9% of the individuals interviewed. A positive patch test result for rubber additives was seen in only 6.6%. Glove‐related urticaria, rhinoconjunctivitis and/or asthma were reported in 24.6% of all cases. Confirmation of an IgE‐mediated reaction was achieved in 8.3% by prick test with glove extracts and 5.0% by RAST No reaction to glove powder was noticed in patch testing or in prick testing. A high prevalence rate of glove‐related symptoms and NRL Type I allergy was found in laboratory workers exposed to rubber gloves. Surprisingly, there was no co‐existence of Type I and Type IV allergy in this population.

Influence of processing and in vitro digestion on the allergic cross-reactivity of three mealworm species

Edible insects are currently being evaluated as an alternative and more sustainable protein source for humans. The introduction of new food sources can lead to development of novel allergies. Because in the Western world, insects are unlikely to be consumed raw, it is important to know how processing and in vitro digestion might influence their allergenicity. Three edible mealworm species (Tenebrio molitor, Zophobas atratus and Alphitobius diaperinus) subjected to processing and in vitro digestion were analysed for IgE cross-reactivity. Immunoblot and MALDI-MS/MS analyses revealed that IgE from crustaceans or House dust mite (HDM) allergic patients showed cross-reactivity to mealworm tropomyosin or α-amylase, hexamerin 1B precursor and muscle myosin, respectively. Heat processing as well as in vitro digestion did diminish, but not eliminate, HDM or tropomyosin IgE cross-reactivity. Results show that individuals allergic to HDM or crustaceans might be at risk when consuming mealworms, even after heat processing.

Multicentre double-blind placebo-controlled food challenge study in children sensitised to cashew nut

Background Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. Methods and Findings A total of 179 children were included (median age 9.0 years; range 2–17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. Conclusion This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. Trial Registration www.ncbi.nlm.nih.gov/pubmed NTR3572

Purification and Characterization of Anacardium occidentale (Cashew) Allergens Ana o 1, Ana o 2, and Ana o 3.

In this study a fast and simple purification procedure for the three known allergens from cashew (7S globulin Ana o 1, 11S globulin Ana o 2, and 2S albumin Ana o 3) is described. The purified allergens are characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, glycoprotein stain, and protein identification. The purified proteins still bind IgE, and this IgE binding varied between different pools of patient serum. Ana o 1 was found to be a glycoprotein. Ana o 3 has been studied more in detail to identify both the small and large subunits, both displaying microheterogeneity, and epitope mapping of Ana o 3 has been performed.

Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

Background: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome‐wide association study and meta‐analysis. Objective: We sought to investigate genetic susceptibility to PA. Methods: Eight hundred fifty cases and 926 hyper‐control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome‐wide association study to identify susceptibility variants for PA in the Canadian population. A meta‐analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n=2), Australian, German, and Dutch (n=2) populations. Results: An SNP near integrin &agr;6 (ITGA6) reached genome‐wide significance with PA (P=1.80×10−8), whereas SNPs associated with Src kinase–associated phosphoprotein 1 (SKAP1), matrix metallopeptidase 12 (MMP12)/MMP13, catenin &agr;3 (CTNNA3), rho GTPase–activating protein 24 (ARHGAP24), angiopoietin 4 (ANGPT4), chromosome 11 open reading frame (C11orf30/EMSY), and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association (P≤1.49×10−6). In the meta‐analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, C11orf30, and EXOC4 were significant (P≤1.49×10−6). When a phenotype of any food allergy was used for meta‐analysis, the C11orf30 locus reached genome‐wide significance (P=7.50×10−11), whereas SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, and EXOC4 and additional C11orf30 SNPs were suggestive (P≤1.49×10−6). Functional annotation indicated that SKAP1 regulates expression of CBX1, which colocalizes with the EMSY protein coded by C11orf30. Conclusion: This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.

Maternal psychiatric symptoms during pregnancy and risk of childhood atopic diseases

Maternal psychiatric symptoms during pregnancy might affect the developing immune system and subsequent risk of childhood atopic diseases.

Threshold dose distribution and eliciting dose of cashew nut allergy

A previous study1 found that 137 of 179 cashew nut sensitized (nausea, vomiting, stomach pain, and diarrhea) (72%), followed by children (76.5%) suspected of having cashew nut allergy had a positive double-blind, placebo-controlled food challenge (DBPCFC result), with 63 of 137 children (46%) manifesting subjective and/or objective symptoms to the lowest dose (1 mg of cashew nut protein). The primary aim of this study was to determine the distribution of threshold doses and the eliciting doses (EDs) in this population. The secondary aimwas to investigate whether children who reacted to 1 mg of cashew nut (n 1⁄4 63) could react to even lower doses than 1 mg (low-dose follow-up study). The children participated in the Improvement of Diagnostic Methods for Allergy Assessment (IDEAL; trialregister.nl Identifier: NTR3572). The inclusion and exclusion criteria and detailed study protocol with stop criteria for the DBPCFC were previously described.1 Briefly, we measured sensitization (specific IgE [sIgE] and skin prick test [SPT]) with cashew nut extract and performed DBPCFC tests with an 8-step incremental dose regimen (1, 3, 10, 30, 100, 300, 1,000, and 1,736 mg of cashew nut proteins).2 All children who reacted to 1mg of cashewnut in the IDEAL studywere asked to participate in a low-dose follow-up study, which consisted of a DBPCFC with a 6-step incremental dose regimen, starting with 0.01 mg, followed by increasing doses of 0.03, 0.10, 0.30, 1, and 3 mg of cashew protein, performed between 4 and 30 months after the initial IDEAL challenges. The low-dose challenge results were considered positive if objective or subjective symptoms occurred. Therewere no stop criteria, and all patients completed the low-dose DBPCFC test to step 6, unless notmedically justified or unethical or if the patient refused to continue the test. To facilitate theweighing of these small doses, ground cashew nuts were diluted 1:10 with granulated sugar, according to the technical method of Taylor et al.3 The Interval-Censoring Survival Analysis approach was used to analyze the no observed adverse effect level and lowest observed adverse effect level intervals for each allergic individual as described previously.4 The SAS LIFEREG procedure, version 9.2 (SAS Institute Inc, Cary, North Carolina), was used to fit the log-normal, log-logistic, and Weibull parametric distributions based on cumulative doses for this cashew allergic population, and 95% CIs were calculated. The EDs were determined.4 The patient characteristics and diagnostic results of the 179 participating children of the IDEAL study were previously described.1 The median age of the children was 9.0 years (range, 2e17 years), with 106 boys (59%) and 73 girls (41%). Themedian sIgE cashewwas 3.72 kU/L (range, 0e 100 kU/L). Themedian histamine equivalent prick index area of cashew SPT was 3.02 (range, 0e15.16).5 Most children experienced gastrointestinal symptoms

Canadian genome-wide association study and meta-analysis confirm HLA as a risk factor for peanut allergy independent of asthma

_To the Editor:_ Previously, we identified the HLA region as a risk factor forpeanut allergy (PA); this observation is supported further by 2 independent genome-wide association studies (GWASs). The HLA class II genes (including HLA-DR, HLA-DQ, and HLADP) encode molecules involved in presentation of extracellular antigens, such as peanut allergens, to T lymphocytes, which in turn mediates B-cell antibody production.We used the Canadian Peanut Allergy Registry (CanPAR) and the Busselton Health Study to conduct the largest GWAS for PA to date. Here we report analysis of the HLA region and a meta-analysis with data from 6 additional studies, which confirms and narrows the region of interest to HLA-DQB1 and establishes independence from asthma loci. [...]

Prediction of cashew nut allergy in sensitized children

combined profile of these six eicosanoids (0.913) was significantly larger than bronchial hyperresponsiveness (BHR, estimated by Δ% FEV1) and FeNO (0.765 and 0.826). The analysis of the ROC curve with Youden Index for pattern eicosanoid profiles indicated the value of 0.514 as having the strong discriminatory ability. At this cutoff value, 35 of 39 asthmatic children were correctly classified, as well as 21 of 27 healthy subjects, giving a sensitivity of 89.7% and specificity of 90.2%. In summary, this study demonstrated excessive concentration of eicosanoids in asthmatic children, making them useful and valuable biomarkers for pediatric asthma. The pattern eicosanoids profiles, which take into account levels of PGD2, 6ketoPGF1α, TXB2 LTE4, 5HETE, and 15HETE, allowed highly accurate discrimination of asthmatic and control children. In fact, there is still a lack of appropriate diagnostic and monitoring tool for pediatric asthma. It seems that the measurement of serum eicosanoid profiles is probably a helpful diagnostic tool for pediatric asthma. However, the assessment of serum eicosanoids does not yet seem to be practically applicable in routine clinical workup because of the limited availability of expensive equipment. Instead, it might be a nice approach for early warning of asthmatic risk, as well as the progress of asthma. Zhi-Gang Gong1 Jin Liu2,3 Guo-Chang Yin1 Yong-Jiang Xu2,4 1Key Lab of Training, Monitoring and Intervention of Aquatic Sports of General Administration of Sport of China, Faculty of Physical Education, Jiangxi Normal University, Nanchang, China 2Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 3Shanghai Pudong Women and Children Hospital, Shanghai, China 4Department of Medicine, University of California San Diego, La Jolla, California, United States E-mail: yjxutju@gmail.com REFERENCES