The Activation Pattern of Drug-Reacting T Cells Has an Impact on the Clinical Picture of Hypersensitivity Reactions.

Rationale β-lactam antibiotics cause drug hypersensitivity reactions (DHR) with various clinical pictures from minor affections like maculopapular exanthema (MPE) and urticaria to severe cutaneous adverse reactions and anaphylaxis. Currently, two different reactivity patterns have been shown to initiate an immune reaction by activating T cells-the hapten concept and the pharmacological interaction with immune receptor (p-i) concept. Objectives In this study, the relationship between the reactivity pattern of drug-reacting T cells of drug allergic patients and their clinical picture has been investigated. Findings Drug-reacting T-cell clones (TCCs) were isolated from patients hypersensitive to β-lactams. Analysis of their reactivity pattern revealed an exclusive use of the hapten mechanism for patients with immediate reactions and for patients of MPE. In patients suffering from drug reactions with eosinophils and systemic symptoms, a severe DHR, analysis of isolated drug-reacting TCC identified the p-i concept as the unique mechanism for T-cell activation. Conclusions The results show a shift from hapten pattern in mild allergic reactions to p-i pattern in severe life-threatening allergic reactions. They strongly argue against the current preclinical risk evaluation of new drugs based on the ability to form haptens

Managing food allergy: GA2LEN guideline 2022

Food allergy affects approximately 2–4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy. + Graphical abstrac

INFOGEST Digestion Assay of Raw and Roasted Hazelnuts and Its Impact on Allergens and Their IgE Binding Activity

Most of the food allergens sensitized via the gastrointestinal tract resist thermal treatments and digestion, particularly digestion by pepsin. Roasted hazelnuts are more commonly consumed than raw ones. Since no studies have characterized gastric digestion protein fragments of raw and roasted hazelnuts nor their IgE binding properties, we compared these aspects of raw and roasted hazelnuts’ gastric digesta obtained by INFOGEST protocol. Their electrophoretically resolved profiles were probed with hazelnut allergic patients’ sera in 1D and 2D immunoblots. Electrophoretic profiles demonstrated pepsin digestion of all hazelnut allergens to varying extents. While 2D immunoblots indicated that roasting slightly reduced allergenicity, IgE ELISA with the pool of sera showed a slight significant (10%) increase in IgE binding in both gastric digesta. Cor a 9 isolated from the raw and roasted hazelnuts, characterized by far and near CD, remained stable after roasting, with preserved IgE reactivity. Its immunoreactivity contribution by inhibitory ELISA was noticeable in raw and roasted hazelnut digesta; its activity was slightly stronger in the roasted preparations. Roasting has a visible impact on proteins; however, it did not affect overall IgE reactivity. Gastric digestion slightly increases the overall IgE reactivity in raw and roasted hazelnuts, and may therefore impact the profiles of allergens and their fragments available to interact with the immune system in the small intestine

Contact sensitization to essential oils: IVDK data of the years 2010–2019

Background: Essential oils (EOs) are widely used in cosmetics, perfumes, massage fluids, aroma therapy and natural medicine. Some EOs contain contact sensitizers. Objectives: To describe the frequency of sensitization to EOs in dermatitis patients presenting in skin clinics including concomitant reactions, to evaluate the EO patch test preparations and to identify patient groups with an increased risk of EO sensitization. Patients and methods: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010-2019. Results: Twelve EOs were patch tested in an aimed manner in 10 930 patients, of whom 908 (8.3%) reacted to at least 1 EO. Only 6 EOs elicited more than 1% positive patch test reactions: ylang ylang (I + II) oil (3.9%), lemongrass oil (2.6%), jasmine absolute (1.8%), sandalwood oil (1.8%), clove oil (1.6%) and neroli oil (1.1%). Concomitant reactions among EOs or to EOs and fragrances were frequent. Among EO-positive patients, women, leg dermatitis patients, patients aged 40 years or more, masseurs and cosmeticians were over-represented. Conclusions: Sensitization to EOs occurs, albeit infrequently in most cases. Masseurs and cosmeticians have an increased risk of sensitization to EOs. Keywords: clinical epidemiology; contact allergy; essential oils; fragrances; patch testin

Threshold Dose for Shrimp: A Risk Characterization Based on Objective Reactions in Clinical Studies

A DBPCFC [double-blind, placebo-controlled food challenge] of shrimp-allergic adults was conducted to obtain individual threshold doses. Results of this study and published research were combined and a population threshold for shrimp was determined from dose-distribution modeling. The shrimp-allergic population seems to have a higher threshold compared to other populations for other food allergens. Additional shrimp challenges should be done to confirm these initial results

The Utility of an International Sera Bank for Use in Evaluating the Potential Human Allergenicity of Novel Proteins

In the safety assessment of novel foods produced through biotechnology, careful consideration is given to determining the allergenic potential of newly introduced proteins. IgE serum screening is one tool for evaluating whether the protein in question has sequence identity to a known allergen or if the source of the gene encoding the protein is a known allergenic food. A "specific” serum screen involves testing a gene product with sera from patients with documented clinical allergy to a specific allergen to confirm that the gene product of interest is not the same protein to which the patient produces IgE antibodies. A "targeted” serum screen involves testing the gene product of interest with sera from patients sensitive to food or aeroallergens from the same broad group. The concept of a global sera bank with accessible, well-characterized sera for use in such assays is an appealing option. This paper summarizes the consensus elements from a workshop to evaluate the potential utility of an international sera bank for evaluating the allergenicity of novel proteins. Areas of agreement following the workshop included the following: (1) specific sera screens are appropriate for exploring potentially cross-reactive proteins that have been identified through bioinformatics analyses; however, additional validation is needed, particularly for targeted sera screens, (2) practical and ethical considerations may preclude the formation of a global sera bank, and therefore, (3) a regional network of clinicians who could serve as sources of patient sera or be approached to conduct sera studies would be the most practical alternativ

Targeting Ara h 2 with human‐derived monoclonal antibodies prevents peanut‐induced anaphylaxis in mice

Background: Peanut allergy is a type‐I hypersensitivity immune reaction mediated by the binding of peanut allergens to IgE‐FcεRI complexes on mast cells and basophils and by their subsequent cellular degranulation. Of all major peanut allergens, Ara h 2 is considered the most anaphylactic. With few options but allergen avoidance, effective treatment of allergic patients is needed. Passive immunotherapy (herein called PIT) based on prophylactic administration of peanut‐specific monoclonal antibodies (mAbs) may present a promising treatment option for this under‐served disease. Method: Fully human recombinant anti‐peanut IgG mAbs were tested in mice sensitized to peanut allergen extract. Allergic mice received intravenous immunotherapy with anti‐peanut Ara h 2‐specific IgG1 or IgG4 mAbs cocktails, and were then challenged by a systemic injection of high‐dose peanut allergen extract. The protection from allergic anaphylaxis was measured by monitoring the core body temperature. Results: PIT with peanut‐specific mAbs was associated with a significant and dose‐dependent reduction of anaphylactic reactions in peanut‐sensitized mice challenged with peanut allergen extract. Complete protection was observed at doses approximately 0.3–0.6 mg mAbs. Mixtures of mAbs were more effective than single mAbs, and effective treatment could be obtained with mAbs of both IgG1 and IgG4 subclasses. The therapeutic effect of anti‐Ara h 2 mAbs was based on allergen neutralization and independent of the Fcγ receptor and mast‐cell inhibition. Conclusion: This is the first report that shows that human‐derived anti‐peanut mAbs can prevent allergic anaphylaxis in mice. The study demonstrates that neutralizing allergenic epitopes on Ara h 2 by mAbs may represent a promising treatment option in peanut‐allergy