Allergies, Volume 5, Issue 1 (March 2025) – 8 articles

Background: Tree nut allergy affects approximately 1% of the U.S. population and the prevalence is increasing. Walnut allergy is the most commonly reported tree nut allergy in the United States. This study aimed to investigate the IgE cross-reactivity between walnut allergen Jug r 4 and peanut allergen Ara h 3 in individuals with dual walnut and peanut allergies. Methods: Jug r 4 was purified from whole walnut extract and analyzed via western blot using anti-Ara h 3 antibodies alongside serum IgE from walnut allergic patients. Sera from individuals allergic to both peanuts and walnuts were utilized to examine peptide microarrays comprising synthetic overlapping 15 mer peptides, offset by five amino acids, of Ara h 3 and Jug r 4. These results were compared against computationally predicted IgE epitopes using the Structural Database for Allergic Proteins (SDAP). Additionally, SWISS-MODEL protein modeling software was employed to map IgE epitopes onto Ara h 3 and Jug r 4. Results: Our findings revealed previously unreported IgE epitopes for dual-allergic sera within both allergens, highlighting the locations of empirically determined and SDAP-predicted IgE epitopes. Conclusions: While six epitopes were predicted as cross-reactive, only three were frequently recognized by IgE in dual-allergic individuals, underscoring their potential significance in clinically relevant cross-reactivity. Full article

In Switzerland, only scarce data are available on the prevalence and treatment of allergic rhinitis. Although the presence of AR symptoms in temporal relation to the respective aeroallergen is indicative, still a substantial number of affected individuals are deemed underdiagnosed and potentially undertreated. A national online survey was conducted for consecutive participants with AR symptoms in medical practices irrespective of diagnosis, therapy, or the reason for the visit. Univariate and multivariate regression analyses were performed, as well as multiple correspondence analysis for participants with allergic rhinitis diagnosis (ARwD) and without diagnosis (ARwoD). A total of 392 of 637 participants with rhinitic symptoms self-reported an AR diagnosis with a symptom onset more than 5 years ago in 74%. Despite treatment, up to one-third of participants with ARwD had persistent severe symptoms. Asthma was reported more frequently in participants with ARwD (148/392) than with ARwoD (26/245), (42% vs. 12%, p < 0.001, q < 0.001). Allergologists were consulted more often by participants with ARwD (106/392; 30% vs. 3/245; 2%), while more participants with ARwoD visited pharmacies for treatment advice (40/392; 11% vs. 57/245; 40%). The coexistence of AR and asthma with severe symptoms is a specific phenotype with difficult to treat nasal symptoms, amongst others. Hence, appropriate diagnosis and treatment of suspected and diagnosed AR should be prioritized, especially, but not limited to, patients with AR and asthma. Full article

Regulatory T cells (Tregs) play a central role in immune regulation and tolerance. The transcription factor FOXP3 is a master regulator of Tregs in both humans and mice. Mutations in FOXP3 lead to the development of IPEX syndrome in humans and the scurfy phenotype in mice, both of which are characterized by fatal systemic autoimmunity. Additionally, Treg dysfunction and FOXP3 expression instability have been implicated in nongenetic autoimmune diseases, including graft-versus-host disease, inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. Recent investigations have explored FOXP3 expression in allergic diseases, revealing Treg alterations in food allergies, asthma, and atopic dermatitis. This review examines the multifaceted roles of FOXP3 and Tregs in health and various pathological states, including autoimmune disorders, allergic diseases, and cancer. Additionally, this review focuses on the impact of recent technological advancements in facilitating Treg-mediated cell and gene therapy approaches, including CRISPR/Cas9-based gene editing. The critical function of FOXP3 in maintaining immune homeostasis and tolerance to both self-antigens and alloantigens is emphasized. Considering the potential involvement of Tregs in allergic diseases, pharmacological interventions and cell-based immunomodulatory strategies may offer promising avenues for developing novel therapeutic approaches in this field. Full article

Peanut allergy, a significant public health issue, poses challenges due to its potential for life-threatening anaphylaxis and profound impact on quality of life. Traditional management approaches, including allergen avoidance and epinephrine administration, are effective in mitigating acute symptoms but do not address the underlying allergy or long-term disease burden. Recent advances in immunotherapy and biologics, as well as innovative technologies such as gene editing and microbiome modulation, have introduced promising pathways for desensitization and sustained unresponsiveness. This review provides a comprehensive exploration of emerging therapies for peanut allergy, including oral, sublingual, and epicutaneous immunotherapy, biologic agents, gene-editing techniques, and novel drug therapies. We discuss their mechanisms, clinical efficacy, and associated challenges, emphasizing the potential for these innovations to revolutionize peanut allergy treatment. Despite significant progress, barriers such as adverse reactions, cost, and limited access remain. Addressing these challenges through further research and standardization could transform the future of peanut allergy management. Full article

Peanut allergy presents a significant and growing public health concern, marked by its increasing prevalence and potential for severe allergic reactions. Traditional diagnostic methods, such as skin prick testing and serum IgE assays, serve as cornerstone approaches but often fall short in specificity, sensitivity, and risk stratification. This has driven the development of innovative diagnostic technologies, including component-resolved diagnostics, basophil activation tests, bead-based epitope assays, molecular diagnostics, and artificial intelligence applications. These advancements promise greater diagnostic precision, improved patient stratification, and tailored management strategies. However, challenges such as high costs, accessibility issues, and the need for standardized protocols hinder their widespread clinical adoption. This review explores the evolution of peanut allergy diagnostics, comparing traditional and emerging methodologies, and discusses their clinical implications, limitations, and future directions. The integration of advanced technologies with established approaches holds the potential to revolutionize peanut allergy diagnosis and management, ultimately enhancing patient care and outcomes. Full article

Background/Objectives: Hereditary angioedema (HAE) is a rare genetic condition marked by recurring episodes of intense swelling that affect the skin, gastrointestinal system, and airways. Lanadelumab, a monoclonal antibody that inhibits plasma kallikrein, is approved for long-term prophylaxis (LTP) in HAE patients, and has shown substantial efficacy in reducing disease symptoms. This single-center, retrospective study analyzed the real-world impact of lanadelumab on healthcare resource utilization, angioedema episode frequency, and quality of life (QoL) among adult HAE patients treated at the allergy department of Hospital Universitario de Canarias, Tenerife, Spain. Methods: This study included patients with a confirmed diagnosis of bradykinin-mediated HAE type 1 who were receiving lanadelumab 300 mg subcutaneously every two weeks, meeting specific inclusion criteria. A retrospective review of medical records from March 2021 to June 2024 assessed clinical outcomes under lanadelumab therapy, compared to prior clinical status. Key metrics included angioedema attack frequency, use of on-demand icatibant treatment, hospital visits, and QoL using the HAE-QoL questionnaire, alongside any adverse reactions associated with lanadelumab. Results: The investigation revealed a 75.3% reduction in hospital visits and a 94.1% decrease in angioedema episodes among HAE patients. Additionally, use of on-demand rescue medication (icatibant) was reduced by 61% (p < 0.05), while quality of life (QoL) scores improved from 62.2 to 99.5, with no significant adverse effects reported. Conclusions: Lanadelumab significantly reduced healthcare resource use and angioedema episodes, with marked improvements in quality of life. The reduced need for on-demand medication and hospital visits highlights lanadelumab’s value as an effective long-term prophylactic treatment with minimal adverse effects for HAE patients in real-world settings. Full article

Seafood is a crucial source of nutrients, with global consumption steadily increasing. Among seafood-related allergies, shellfish are a significant cause of food allergy and anaphylaxis worldwide, affecting approximately 0.5–2.5% of the general population. While the majority of existing research has focused on crustaceans, allergic reactions to mollusks, including their clinical characteristics, remain poorly understood. In the Canary Islands, limpets (a type of marine gastropod) are widely consumed as part of the traditional cuisine. Despite isolated reports of limpet allergy, no large-scale studies or comprehensive clinical analyses have been published on this topic. A cohort of patients sensitized to limpets was analyzed: 66 patients were monosensitized to limpets (Group A), while 64 patients demonstrated additional sensitization to other shellfish (Group B). Limpet ingestion was associated with delayed and severe symptoms, including anaphylaxis and severe asthma. Notably, only 11.5% of patients in Group A tested positive for shellfish allergens using ALEX testing compared to 67.9% in Group B. The identification of protein bands in the 25–40 and 50–200 kDa molecular weight ranges in monosensitized patients provides a novel finding that differentiates this study from prior research. Our study represents the largest reported series of patients with documented limpet allergy to date. Full article

In vitro tests of cellular activity form part of the diagnostic algorithm of drug hypersensitivity reactions. Because of the wide range of pharmacological mechanisms, clinical symptoms, genetic components, and laboratory tests involved, it is important to know how a particular test performs in the diagnostic procedure. We carried out a detailed retrospective analysis of more than 6000 measurements of numerous drug compounds tested in 738 serum samples over the past 6 years. Our cell viability-based lymphocyte transformation had a coefficient of variation of 10% and showed similar performance over the whole range of tested ages. With an adequate number of parallel measurements, the test can identify modest increases in stimulation indices with high confidence. Similar percentages of analytically positive responses (11.4%, 13.5%, and 9.7%) were observed for the three most frequently tested drug groups, namely, antibiotics, non-steroid anti-inflammatory agents, and anesthetics. These results confirm that cell viability tests are suitable alternatives for proliferation assays in drug allergy testing. Full article