Basophil Activation to Gluten and Non-Gluten Proteins in Wheat-Dependent Exercise-Induced Anaphylaxis

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a cofactor-induced wheat allergy. Gluten proteins, especially ω5-gliadins, are known as major allergens, but partially hydrolyzed wheat proteins (HWPs) also play a role. Our study investigated the link between the molecular composition of gluten or HWP and allergenicity. Saline extracts of gluten (G), gluten with reduced content of ω5-gliadins (G-ω5), slightly treated HWPs (sHWPs), and extensively treated HWPs (eHWPs) were prepared as allergen test solutions and their allergenicity assessed using the skin prick test and basophil activation test (BAT) on twelve patients with WDEIA and ten controls. Complementary sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE), high-performance liquid chromatography (HPLC), and mass spectrometry (MS) analyses revealed that non-gluten proteins, mainly α-amylase/trypsin inhibitors (ATIs), were predominant in the allergen test solutions of G, G-ω5, and sHWPs. Only eHWPs contained gliadins and glutenins as major fraction. All allergen test solutions induced significantly higher %CD63+ basophils/anti-FcεRI ratios in patients compared with controls. BAT using sHWPs yielded 100% sensitivity and 83% specificity at optimal cut-off and may be useful as another tool in WDEIA diagnosis. Our findings indicate that non-gluten proteins carrying yet unidentified allergenic epitopes appear to be relevant in WDEIA. Further research is needed to clarify the role of nutritional ATIs in WDEIA and identify specific mechanisms of immune activation

Allergologische Diagnostik von Überempfindlichkeitsreaktionen auf Arzneimittel

Überempfindlichkeitsreaktionen auf Arzneimittel müssen ausreichend geklärt werden mit dem Ziel, den Auslöser zu identifizieren. Die Anamnese umfasst neben der allgemeinen Anamnese auch Informationen zu angewandten Arzneimitteln, zur Klassifikation und zu den Umständen der Reaktion. Hauttests erfolgen bei allen Reaktionen mit Symptomen allergischer Überempfindlichkeiten mit geeigneten Testkonzentrationen, möglichst zwischen 4 Wochen und 6 Monate nach Abheilung der Reaktion durch Pricktest, Intrakutantest, Epikutantest oder Photopatchtest. Validierte Tests zum Nachweis spezifischer IgE-Antikörper im Serum sind nur für wenige Arzneistoffe (vor allem Betalaktamantibiotika) verfügbar; andere immunologische Labormethoden, z.B. der Basophilen-Aktivierungstest, werden nur in ausgewählten Fällen angewendet. Provokationstests sind indiziert, wenn der Auslöser durch bisherige Untersuchungen nicht mit Sicherheit identifiziert werden kann. Die Bewertung der Ergebnisse von Provokationstests sollte möglichst anhand objektiver Parameter erfolgen. Das Ergebnis der abschließenden Gesamtbeurteilung wird mit dem Patienten ausführlich besprochen und in einem Allergiepass niedergeleg

Allergologische Diagnostik von Überempfindlichkeitsreaktionen auf Arzneimittel

Drug hypersensitivity reactions have to be tested to identify the culprit substance. The history includes the general information and specific data concerning used drugs, the classification and circumstances of the reaction. Skin tests are performed in all hypersensitivity reactions with allergic symptoms. Tests should be done between four weeks and six months after clearance of the symptoms by performing skin prick test, intradermal test, patch test or photopatch test. Validated tests for the detection of specific IgE antibodies in the serum are available for only few drugs, especially betalactam antibiotics. Other laboratory tests, e.g., the basophil activation test are done only in special cases. Provocation tests are indicated, if the culprit drug cannot be identified by the above mentioned tests. If possible, the evaluation of provocation tests should rely on objective parameters. The concluding assessment will be discussed with the patient and will be documented in an allergy pass

Clinical impact and proposed application of molecular markers, genetic variants, and cytogenetic analysis in mast cell neoplasms: Status 2022

Mast cell neoplasms are an emerging challenge in the fields of internal medicine, allergy, immunology, dermatology, laboratory medicine, and pathology. In this review, we discuss the current standards for the diagnosis and prognostication of mast cell neoplasms with special reference to clinically relevant germline and somatic gene variants. In patients with cutaneous mastocytosis or with indolent systemic mastocytosis (SM), various KIT-activating mutations act as key molecular drivers of the disease. In adults, KIT p.D816V is by far the most prevalent driver, whereas other KIT mutants are detected in nearly 40% of children. In advanced SM, including aggressive SM, SM with an associated hematological neoplasm, and mast cell leukemia, additional somatic mutations in other genes, such as SRSF2, JAK2, RUNX1, ASXL1, or RAS, may be detected. These drivers are more frequently detected in SM with an associated hematological neoplasm, particularly in male patients. Recently, hereditary alpha-tryptasemia has been identified as a genetic trait more prevalent in SM compared with healthy controls. Moreover, hereditary alpha-tryptasemia is more frequent in patients with SM with Hymenoptera venom allergy and severe mediator-related symptoms than in patients with SM without symptoms. On the basis of this knowledge, we propose a diagnostic algorithm in which genetic markers are applied together with clinical and histopathologic criteria to establish the diagnosis and prognosis in SM

A position paper from German and Austrian Allergy Societies AeDA, DGAKI, GPA and ÖGAI

Background: For the preventive treatment of the 2019 coronavirus disease (COVID-19) an unprecedented global research effort studied the safety and efficacy of new vaccine platforms that have not been previously used in humans. Less than one year after the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral sequence, these vaccines were approved for use in the European Union (EU) as well as in numerous other countries and mass vaccination efforts began. The so far in the EU approved mRNA vaccines BNT162b2 and mRNA-1273 are based on similar lipid-based nanoparticle carrier technologies; however, the lipid components differ. Severe allergic reactions and anaphylaxis after COVID-19 vaccination are very rare adverse events but have drawn attention due to potentially lethal outcomes and have triggered a high degree of uncertainty. Methods: Current knowledge on anaphylactic reactions to vaccines and specifically the new mRNA COVID-19 vaccines was compiled using a literature search in Medline, PubMed, as well as the national and international study and guideline registries, the Cochrane Library, and the Internet, with special reference to official websites of the World Health Organization (WHO), US Centers for Disease Control and Prevention (CDC), Robert Koch Institute (RKI), and Paul Ehrlich Institute (PEI). Results: Based on the international literature and previous experience, recommendations for prophylaxis, diagnosis and therapy of these allergic reactions are given by a panel of experts. Conclusion: Allergy testing is not necessary for the vast majority of allergic patients prior to COVID-19 vaccination with currently licensed vaccines. In case of allergic/anaphylactic reactions after vaccination, allergy workup is recommended, as it is for a small potential risk population prior to the first vaccination. Evaluation and approval of diagnostic tests should be done for this purpose

Personalized management strategies in mast cell disorders: ECNM-AIM User's guide for daily clinical practice

Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma. In most patients with SM, somatic mutations in KIT are detected. Patients with indolent SM have a normal to near-normal life expectancy, whereas patients with advanced SM, including aggressive SM and MC leukemia, have a poor prognosis. In those with advanced SM, multiple somatic mutations and an associated hematologic neoplasm may be detected. Mediator-related symptoms can occur in any type of mastocytosis. Symptoms may be mild, severe, or even life-threatening. In patients with severe acute symptoms, an MC activation syndrome may be diagnosed. In these patients, relevant comorbidities include IgE-dependent and IgE-independent allergies. Management of patients with SM is an emerging challenge in daily practice and requires in-depth knowledge and a multidisciplinary and personalized approach with selection of appropriate procedures and interventions. In this article, we review the current knowledge on SM and MC activation syndrome, with emphasis on multidisciplinary aspects in diagnosis and patient-specific management. In addition, we provide a user’s guide for application of markers, algorithms, prognostic scores, and treatments for use in daily practice.This work was supported in part by the Austrian Science Fund (FWF; projects F4704 and P32470-B to P.V.) and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (to M.C.C. and D.D.M.). The content is solely the responsibility of the authors and does not represent the official views of the NIH

Real-life evaluation of molecular multiplex IgE test methods in the diagnosis of pollen associated food allergy

13 Pág.Diagnosis of food allergies is challenging, as combining information from specific IgE (sIgE)-sensitization pattern and skin prick tests (SPTs) with clinical history is necessary for a personalized management of allergic patients. The aim of this study was to compare two molecular tests, the ImmunoCAP ISAC (ISAC) and the Allergy Explorer, version 2 (ALEX2 ) in the context of pollen food syndrome (PFS) diagnosis in a real-life scenario, to assess the benefit of multiplex testing in PFS patients.This work was financially supported by the H2020 EU project “AllerScreening” (H2020-NMBP-X-KET-2017-768641). EJJ was supported by the Danube Allergy Research Cluster, #08, Vienna and Krems, AustriaPeer reviewe

Standards of genetic testing in the diagnosis and prognostication of systemic mastocytosis in 2022: Recommendations of the EU-US cooperative group

Mastocytosis comprises rare heterogeneous diseases characterized by an increased accumulation of abnormal mast cells in various organs/tissues. The pathogenesis of mastocytosis is strongly linked to the presence of KIT-activating mutations. In systemic mastocytosis (SM), the most frequent mutation encountered is KIT p.D816V, whose presence constitutes one of the minor diagnostic criteria. Different techniques are used to search and quantify the KIT p.D816V mutant; however, allele-specific quantitative PCR and droplet digital PCR are today the most sensitive. The analysis of the KIT p.D816V allele burden has undeniable interest for diagnostic, prognostic, and therapeutic monitoring. The analysis of non–mast cell hematological compartments in SM is similarly important because KIT p.D816V multilineage involvement is associated with a worse prognosis. In addition, in advanced forms of SM, mutations in genes other than KIT are frequently identified and affect negatively disease outcome and response to therapy. Thus, combined quantitative and sensitive analysis of KIT mutations and next-generation sequencing of other recurrently involved myeloid genes make it possible to better characterize the extent of the affected cellular compartments and additional molecular aberrations, providing a more detailed overview of the complex mutational landscape of SM, in relation with the clinical heterogeneity of the disease. In this article, we report the latest recommendations of the EU-US Cooperative Group presented in September 2020 in Vienna during an international working conference, on the techniques we consider standard to detect and quantify the KIT p.D816V mutant in SM and additional myeloid mutations found in SM subtypes.D.D.M., J.J.L., and M.C.C. were supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. P.V. was supported by the Austrian Science Fund (FWF) (grant nos. F4704-B20 and P32470-B)