Ingestive and inhalative allergy to the mushroom Boletus edulis

This is the first report on inhalative and ingestive allergy to the common edible mushroom Boletus edulis ( Be ) (English, edible boletus ; German, Steinpilz, French, bolet ; Italian, porcino or boleto ) belonging to the class Basidiomycetes. Four cases observed in our allergy unit are presented, showing different clinical manifestations of this rare allergy: as an occupational problem or life-threatening anaphylactic reactions after eating Be. In all cases, skin prick-to-prick tests with raw Be were strongly positive; in three cases, specific IgE against Be could be found. The symptoms were reproducible after an inhalation challenge test. It is noteworthy that not only can Basidiomycetes cause airborne allergy but also that edible mushrooms from this class can cause inhalative and intestinal allergy. The two patients with strong anaphylactic reactions demonstrate that Be may have great allergenic potential.     

Food allergen avoidance in primary prevention of food allergy

Approximately 5–10% of children suffer from allergy to one or more foods. Primary prevention through a hypoallergenic diet may reduce the prevalence of food allergy and associated co-morbidity, such as eczema and urticaria. Breastfeeding has many advantages and should be recommended for all children. Those with a history of atopy in the immediate family are at a higher risk and maternal diet during lactation, avoiding highly allergenic foods, may enhance the benefit. Cow's milk should be strictly avoided, and supplements, if required, should be with a hypoallergenic formula. Delayed introduction of egg, nuts, wheat and fish has also been suggested. Dietary restriction may have nutritional consequences for the mother and child and supervision by a dietician is essential. Maternal diet during pregnancy is not advisable as the benefit is minimal and there may be adverse effects on the foetal nutrition. In high risk infants, a combined approach, where breastfeeding with maternal avoidance of highly allergenic foods, supplemented by extensively hydrolysed formula during the first 6 months of life, in addition to the delayed introduction of solid foods, has been shown to reduce the development of food allergy in infants.     

EAACI Guidelines on allergen immunotherapy: IgE‐mediated food allergy

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA‐AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE‐mediated Food Allergy, aims to provide evidence‐based recommendations for active treatment of IgE‐mediated food allergy with FA‐AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post‐discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA‐AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post‐discontinuation is also suggested, but not confirmed. Adverse events during FA‐AIT have been frequently reported, but few subjects discontinue FA‐AIT as a result of these. Taking into account the current evidence, FA‐AIT should only be performed in research centers or in clinical centers with an extensive experience in FA‐AIT. Patients and their families should be provided with information about the use of FA‐AIT for IgE‐mediated food allergy to allow them to make an informed decision about the therapy.     

Kiwifruit allergy: actinidin is not a major allergen in the United Kingdom

BACKGROUND: Actinidin has previously been reported as the major allergen in kiwifruit. Objectives To investigate the relevance of actinidin in a well-characterized population of UK patients with kiwifruit allergy. METHODS: To identify the allergens in kiwifruit, using Western blots, we examined the IgE-binding patterns of 76 patients with a history of kiwifruit allergy, 23 of who had had a positive double-blind, placebo-controlled food challenge. In addition, IgE binding to purified native actinidin was studied in 30 patients, and to acidic and basic isoforms of recombinant actinidin in five patients. Inhibition of IgE binding to kiwifruit protein extract by purified native actinidin was investigated by both inhibition immunoblots and inhibition ELISAs using pooled sera. RESULTS: Twelve protein bands in kiwifruit protein extract were bound by IgE. A protein band with a molecular weight of 38 kDa was the major allergen recognized by 59% of the population. IgE did not bind to actinidin in the kiwifruit protein extract, or to purified native or recombinant forms of actinidin during Western blotting. Pooled sera bound to kiwifruit protein extract but not purified actinidin on ELISA, and pre-incubating sera with actinidin did not inhibit IgE binding to kiwifruit protein extract on immunoblot or ELISA. CONCLUSION: A novel 38 kDa protein, not actinidin, is the major allergen in this large study population. Identification of major allergens in one patient group is therefore not necessarily reproducible in another; therefore, major allergens should not be defined until there is a sufficient body of data from diverse geographical and cultural populations.     

Investigation of the stability of apple allergen extracts

To determine optimal conditions for allergen preservation, we investigated the influence of different stabilizing additives and of storage temperature on the allergen activity of apple protein preparations, obtained by extraction in phosphate buffer or by precipitation in diacetone alcohol and resolubilization in phosphate buffer in the presence or absence of enzyme inhibitors. For this purpose, the extracts were stored for 6 months either in frozen state at −20° C or in lyophilized state at −20° C, 4° C, or room temperature and were characterized by SDS-PAGE, immunoblot, ELISA inhibition, and prick test. The highest stability revealed the extracts that were prepared by precipitation in the organic solvent in the presence of enzyme inhibitors, lyophilized, and stored at −20° C. For storage of extract solutions at 4° C, PBS/glycerol and cysteine/sodium citrate/glycerol were found to be the most effective stabilizing additives.     

Serum basal tryptase may be a good marker for predicting the risk of anaphylaxis in children with food allergy

A relationship between serum basal tryptase (sBT) levels, anaphylactic reactions, and clonal mast cell diseases was shown recently in adults with venom allergy, but the relationship between sBT levels and IgE‐mediated food allergy and anaphylaxis is not known. In this study, children with food allergy (FA; n = 167) were analyzed in two groups according to the presence (FA+/A+; n = 79) or absence of anaphylaxis (FA+/A?; n = 88) and were compared with a control group (n = 113). Median sBT values in FA+/A+, FA+/A?, and control groups were 4.0 ng/ml (2.8–5.8), 3.6 (2.3–4.5), and 3.3 (2.4–4.4), respectively (P = 0.022). sBT measurements higher than the cutoff values of 5.7 and 14.5 were associated with 50% and 90% predicted probabilities, respectively, of moderate to severe anaphylaxis. Children with tree nuts/peanut allergies had significantly higher levels of sBT than children with milk and egg allergy (P = 0.022). Results suggest that sBT levels may predict moderate to severe anaphylaxis in children with food allergy, which may follow a particular pattern according to the food allergy phenotype.     

Allergen immunotherapy for IgE‐mediated food allergy: a systematic review and meta‐analysis

Background

The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE‐mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost‐effectiveness of AIT in the management of food allergy.

Methods

We undertook a systematic review and meta‐analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT‐NRS tool for quasi‐RCTs. Random‐effects meta‐analyses were undertaken, with planned subgroup and sensitivity analyses.

Results

We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty‐five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty‐seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta‐analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease‐specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta‐analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses.

Conclusions

AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE‐mediated food allergy whilst receiving (i.e. desensitization) and post‐discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost‐effectiveness of AIT.     

Clinical usefulness of microarray-based IgE detection in children with suspected food allergy

Background: Component‐resolved diagnostics using microarray technology has recently been introduced into clinical allergology, but its applicability in children with food allergy has hardly been investigated so far. The aim of this study was to evaluate the utility of microarray‐based IgE detection in the diagnostic workup of food allergy and to compare this new diagnostic tool with established methods of allergen‐specific IgE detection. Methods: We investigated 130 infants and children with suspected allergy to cow’s milk (CM) or hen’s egg (HE). Serum IgE measurements, skin prick tests, allergen microarray assays and controlled oral food challenges with HE and CM were performed. Results: We analyzed 145 oral challenges that served as reference parameters for assay performance assessment. On this basis, the panel of microarrayed allergen components was shown to represent a comprehensive repertoire of clinically relevant CM and HE proteins. Additionally, the implemented CM and HE components respectively sufficed for equivalent test performance as compared to the corresponding fluorescence enzyme immunoassay extract and skin testing. However, component‐resolved diagnostics for HE and CM allergy did not make oral food challenges superfluous. Clinical IgE decision points predicting positive oral food challenges could be calculated for both in vitro test methods. Conclusions: Allergen microarrays provide a new tool to diagnose symptomatic CM and HE allergy. They show performance characteristics comparable to the current diagnostic tests and may be indicated in small children in whom only small blood volumes are obtainable. However, they are not capable of replacing double‐blind, placebo‐controlled food challenges in most cases.     

Precautionary allergen labelling: perspectives from key stakeholder groups

Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the possibility of reaction from the unintended presence of allergens in foods. However, in its current form, PAL is counterproductive for consumers with food allergies. This review aims to summarize the perspectives of all the key stakeholders (including clinicians, patients, food industry and regulators), with the aim of defining common health protection and risk minimization goals. The lack of agreed reference doses has resulted in inconsistent application of PAL by the food industry and in levels of contamination that prompt withdrawal action by enforcement officers. So there is a poor relationship between the presence or absence of PAL and actual reaction risk. This has led to a loss of trust in PAL, reducing the ability of consumers with food allergies to make informed choices. The result has been reduced avoidance, reduced quality of life and increased risk‐taking by consumers who often ignore PAL. All contributing stakeholders agree that PAL must reflect actual risk. PAL should be transparent and consistent with rules underpinning decision‐making process being communicated clearly to all stakeholders. The use of PAL should indicate the possible, unintended presence of an allergen in a consumed portion of a food product at or above any proposed action level. This will require combined work by all stakeholders to ensure everyone understands the approach and its limitations. Consumers with food allergy then need to be educated to undertake individualized risk assessments in relation to any PAL present.     

Anaphylaxis: a history with emphasis on food allergy

In the century since Paul Portier and Charles Richet described their landmark findings of severe fatal reactions in dogs re-exposed to venom after vaccination with sea anemone venom, treatment for anaphylaxis continues to evolve. The incidence of anaphylaxis continues to be difficult to measure. Underreporting due to patients not seeking medical care as well as failure to identify anaphylaxis affects our understanding of the magnitude of the disease. Treatment with intramuscular epinephrine continues to be the recommended first-line therapy, although studies indicate that education of both the patients and the medical community is needed. Adverse food reactions continue to be the leading cause of anaphylaxis presenting for emergency care. Current therapy for food-induced anaphylaxis is built on the foundation of strict dietary avoidance, rapid access to injectable epinephrine, and education to recognize signs and symptoms of anaphylaxis. Investigation into therapy with oral and sublingual immunotherapy as well as other modalities holds hope for improved treatment of food-induced anaphylaxis.     

From trained immunity in allergy to trained immunity-based allergen vaccines

Innate immune cells experience long lasting metabolic and epigenetic changes after an encounter with specific stimuli. This facilitates enhanced immune responses upon secondary exposition to both the same and unrelated pathogens, a process termed trained immunity. Trained immunity-based vaccines (TIbV) are vaccines able to induce innate immune memory, thus conferring heterologous protection against a broad range of pathogens. While trained immunity has been well documented in the context of infections and multiple immune-mediated diseases, the role of innate immune memory and its contribution to the initiation and maintenance of chronic allergic diseases remains poorly understood. Over the last years, different studies attempting to uncover the role of trained immunity in allergy have emerged. Exposition to environmental factors impacting allergy development such as allergens or viruses induces the reprogramming of innate immune cells to acquire a more pro-inflammatory phenotype in the context of asthma or food allergy. Several studies have convincingly demonstrated that prevention of viral infections using TIbV contributes to reduce wheezing attacks in children, which represent a high-risk factor for asthma development later in life. Innate immune cells trained with specific stimuli might also acquire anti-inflammatory features and promote tolerance, which may have important implications for chronic inflammatory diseases such as allergies. Recent findings showed that allergoid-mannan conjugates, which are next generation vaccines for allergen-specific immunotherapy (AIT), are able to reprogram monocytes into tolerogenic dendritic cells by mechanisms depending on metabolic and epigenetic rewiring. A better understanding of the underlying mechanisms of trained immunity in allergy will pave the way for the design of novel trained immunity-based allergen vaccines as potential alternative strategies for the prevention and treatment of allergic diseases.     

食物过敏患儿食物变应原检测及外周血一般免疫指标分析

目的了解食物过敏儿童常见食物变应原的种类及其构成比、一般体液免疫及细胞免疫状况,为临床采取合理的诊疗措施提供科学依据。方法对246例食物过敏儿童和192例健康儿童血清的14种食物过敏原特异性IgE、血清免疫球蛋白总IgE、IgG、IgA、IgM、补体C3、C4进行检测,并进行外周血淋巴细胞亚群流式细胞术检测,对两组结果进行统计学分析。结果变应原阳性率前5位的分别是牛奶（21.11%）,牛肉（17.20%）,全蛋（16.49%）,黄豆（9.73%）,芝士8.77%。食物过敏组患儿总IgE水平、CD19＋B淋巴细胞水平明显高于健康对照组（P〈0.05）,两组间IgG、IgA、IgM、补体C3、C4水平差异无统计学意义（P〉0.05）,各类型T淋巴细胞（包括CD3＋T淋巴细胞、CD3＋CD4＋辅助T细胞、CD3＋CD8＋抑制T细胞、CD3-CD16＋CD56＋NK细胞水平差异无统计学意义（P〉0.05）。结论广州地区儿童食物过敏的变应原中最常见的是牛奶、牛肉和全蛋,血清总IgE水平、外周血CD19＋B淋巴细胞水平等反映体液免疫功能指标的检测在儿童食物过敏诊断和治疗中的应用值得进一步研究。     

EpidemAAITO: Features of food allergy in Italian adults attending allergy clinics: a multi-centre study

Background Studies of the prevalence of different types of food allergy in adults are lacking.
Objective To define the prevalence of IgE-mediated food allergies in Italian adults attending allergy clinics and to assess possible differences associated with geographical position and/or dietary habits.
Methods Seventeen allergy outpatient clinics scattered throughout Italy participated to a multi-centre study in 2007. The number of atopic subjects and of food allergic patients along with clinical features were recorded by pre-defined criteria. Patients with unequivocal history of food allergy confirmed by positive skin prick test were included as cases.
Results Twenty five thousand six hundred and one subjects were screened; 12 739 (50%) were atopic, and 1079 (8,5%) had IgE-mediated food allergy. Sixty four percent of patients were females. Overall, the most frequent food allergy was the pollen–food allergy syndrome (55%), which was associated with oral allergy syndrome in 95% of cases and whose frequency decreased southbound. Forty-five percent of patients had a type 1 food allergy, in most cases (72%) caused by fruits and vegetables, and generally associated with a history of systemic symptoms. Type 1 food allergies represented 96% of food allergies in the South. Lipid transfer protein (LTP) accounted for 60% of sensitizations and caused most primary food allergies in all areas.
Conclusion Plant-derived foods cause most food allergies in Italian adults. The pollen–food allergy syndrome is the most frequent type of food allergy followed by allergy to LTP whose frequency increases southbound. The pattern of allergy to certain foods is clearly influenced by specific geographic features such as pollen exposure and dietary habits.     

Identification of Pru du 6 as a potential marker allergen for almond allergy

Background

Oral food challenges have demonstrated that diagnosis of almond allergy based on extract-sIgE tests displays low specificity. Molecular allergy diagnosis is expected to improve accuracy, but its value in diagnosing almond allergy remains unknown. The aim of this study was to identify relevant almond allergens and examine their ability to improve almond allergy diagnosis.

Methods

IgE-reactive proteins were purified from almond kernels. IgE binding to almond extract and the allergens was analyzed by quantitative ELISA using sera from 18 subjects with a proven almond allergy. The control group consisted of sera from 18 subjects allergic to peanut and/or tree nuts but tolerant to almond.

Results

Three IgE-binding proteins were identified: legumin (Pru du 6), alpha-hairpinin (Pru du 8), and mandelonitrile lyase (Pru du 10). Positive IgE (≥0.35 kU/L) to almond extract showed 94% sensitivity but only 33% specificity. IgE to Pru du 6 maintained high sensitivity (83%) and provided superior specificity (78%). Sera from almond-allergic subjects had significantly higher IgE levels to almond extract (P < .0001) and Pru du 6 (P < .0001) than sera from tolerant donors. Sensitization to Pru du 6 was highly specific for almond allergy, while frequencies of sensitization to legumins from peanut, walnut, hazelnut, and cashew were similar in both groups. IgE to Pru du 8 and Pru du 10 was less sensitive (41% and 67%), but showed specificities of 100% and 61%.

Conclusion

The use of almond allergens markedly increases the diagnostic specificity compared to the extract. Pru du 6 is a potential new molecular marker for almond allergy.

     

Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy

BACKGROUND: We recently described patients with soybean allergy mainly mediated by cross-reactivity to birch pollen allergens. A majority of those patients were reported to have peanut allergy. OBJECTIVE: We sought to study the occurrence of peanut allergy in patients allergic to birch pollen and characterized the Bet v 1-homologous peanut allergen Ara h 8. METHODS: Recombinant Ara h 8 was cloned with degenerated primers and expressed in Escherichia coli. Nine Swiss and 11 Dutch patients with peanut and birch pollen allergy and a positive double-blind, placebo-controlled food challenge result to peanut were investigated for IgE reactivity to birch pollen and purified peanut allergens and cross-reactivity between birch and peanut. Ara h 8 stability against digestion and roasting was assessed by means of RAST inhibition. The IgE cross-linking potency of Ara h 8 was tested on the basis of basophil histamine release. RESULTS: During double-blind, placebo-controlled food challenge, all patients experienced symptoms in the oral cavity, progressing to more severe symptoms in 40% of patients. CAP-FEIA detected recombinant (r) Ara h 8-specific IgE in 85%. IgE binding to Ara h 8 was inhibited by Bet v 1 in peanut extract immunoblotting and in RAST inhibition. In EAST inhibition recombinant rAra h 8 inhibited IgE binding to peanut in 4 of 7 tested patient sera. Antipeanut response was dominated by Ara h 8 in 12 of 17 tested patients. Furthermore, our results demonstrate a low stability of Ara h 8 to roasting and no stability to gastric digestion. Basophil histamine release with rAra h 8 was more than 20% in 5 of 7 tested sera. CONCLUSIONS: Peanut allergy might be mediated in a subgroup of our patients by means of cross-reaction of Bet v 1 with the homologous peanut allergen Ara h 8.