Clinical and Translational Allergy最新文献

Background: Adrenaline auto-injectors (AAI) are underused to treat anaphylaxis. New adrenaline devices are currently under investigation or have been recently marketed. This survey aimed to assess the perspectives from allergy-trained physicians regarding the AAI use and their expectations about new adrenaline devices.

Methods: This electronic survey was created by the European Anaphylaxis Registry and Allergy-Vigilance Network. It was proposed to their participants (March-April 2025) who were asked to rank their responses on a 11-point Likert scale (0: 'not important' to 10: 'very important'). Results are presented as median with interquartile range.

Results: One hundred and seventy-five physicians (allergists, 59.4%) participated in this survey. There were only few barriers to AAI prescriptions. Up to 65% of participants estimated the following features as very important for new adrenaline devices: prolonged shelf life (9 [7-10]), improved storage conditions (9 [5-9]), detailed pharmacokinetic-pharmacodynamic data (8 [7-10]), optimised dose ranging (8 [7-10]), availability in public spaces (8 [7-10]), devices easy to carry (8 [7-9]), needle-free device (8 [6-10]). A history of anaphylaxis treated with > 1 adrenaline injection (7 [4-9]) or admitted to intensive care unit (7 [3-8]) were reported as the most important barriers to use new adrenaline devices. 75% of participants felt that recommendations from allergy societies and more clinical data are important measures to reduce barriers to new adrenaline devices.

Conclusions: Our data provide insights from allergy-trained physicians into AAI limitations and expectations on new adrenaline devices. To advance them, input from allergy societies and more clinical data from anaphylaxis patients are needed.

Background: In the randomised, controlled study Probiotics in the Prevention of Allergy amongst Children in Trondheim (ProPACT), maternal probiotics given from 36 weeks pregnancy until 3 months post-delivery while breastfeeding reduced atopic dermatitis (AD) in the offspring. Previous analysis of T helper (Th) subsets indicated that the preventive effect may be partially mediated through reduced Th22 percentage at 3 months of age.

Objective: To examine the longitudinal effects of maternal probiotics on Th1, Th2, Th17, Th22, and regulatory T cells (Treg) in offspring at 10 days and 2 years of age compared to the previously published 3 months results.

Methods: Pregnant women (n = 415) were randomised to take probiotic milk (Lacticaseibacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis Bb-12 and Lactobacillus acidophilus La-5) or placebo, and their offspring were assessed for AD at 2 years. We analysed the children's blood collected at 10 days (n = 112) and 2 years (n = 156) for Treg and Th subsets using flow cytometry and included the results from the previously analysed 3 months samples (n = 76) in the same study to compare the three timepoints using linear mixed models.

Results: There were no statistically significant differences between T cell populations of the children in the probiotics and placebo groups at 10 days and 2 years.

Conclusion: We previously observed reduced Th22 percentage in the probiotics group at 3 months. However, since the effect was not seen earlier and did not last, it may not be the main reason for AD prevention.

Immune dysregulation has been widely recognized in the international literature as an underlying condition for hematological malignancies and allergic disorders. This commonality has led researchers to study the potential association, positive or negative, between blood cancers and allergy, but the results remain unclear. The cellular and molecular mechanisms underlying allergic inflammation appear to have dual effects on immune surveillance, potentially positively or negatively influencing carcinogenesis in solid tumors. The same mechanisms may also play a role in the genesis of hematological malignancies, but there is little evidence in the literature to support this. In our review, we explored the possible link between the immune pathways involved in allergic responses and the mechanisms underlying hematological malignancies, focusing on Th2 responses, the activity of inflammatory cells, cytokines, and the emerging role of alarmins. Furthermore, our review aims to assess the association between biologics and the risk of neoplastic disease, with a focus on hematological malignancies. A deeper understanding of shared immune dysregulation pathways and the interactions between various cell types could lead to new preventive or therapeutic approaches for patients with hematological malignancies. Understanding the complex roles of various cellular and molecular mediators of Th2 inflammation in stimulating or inhibiting tumor growth could be a key goal of future research, paving the way for innovative targeted therapies, especially at a time when immunotherapy and monoclonal antibody therapies are increasingly important and effective.

Background: Understanding cell death pathways is critical for elucidating the mechanisms underlying inflammation in atopic dermatitis (AD). This study investigates the role of disulfidptosis, a novel form of programmed cell death, in AD pathogenesis.

Methods: RNA-seq datasets GSE193309 and GSE121212 from GEO were analyzed to examine 43 disulfidptosis-related genes. Differentially expressed genes (DEGs) were identified using the limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to annotate biological functions and signaling pathways. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to identify gene modules significantly associated with AD. A protein-protein interaction (PPI) network was constructed using STRING data, and further visualized and analyzed with Cytoscape to identify core mRNA-pathway relationships involving disulfidptosis. Key disulfidptosis-related mRNAs were validated in the dataset GSE121212. Following house dust mite (HDM) extract treatment, disulfidptosis was induced in HaCaT cells, with characteristic F-actin collapse visualized by confocal microscopy and redox imbalance confirmed by an increased NADP⁺/NADPH ratio. Expression of disulfidptosis-related genes was quantified via RT-qPCR.

Results: A total of 4239, 3570, and 516 DEGs were identified between lesional skin (LS) and healthy control (HC), LS and non-lesional skin (NL), and NL and HC, respectively. WGCNA clustered these DEGs into 14 co-expression modules, five of which were significantly correlated with AD. Notably, the turquoise module showed the strongest association with LS and contained four disulfidptosis-related genes: ACTB, GYS1, SLC7A11, and MYH9. These four genes were consistently upregulated in LS compared to both NL and HC. Immunofluorescence staining showed F-actin contraction and membrane detachment in HDM-treated HaCaT cells, consistent with disulfidptotic morphology. A significant increase in the NADP⁺/NADPH ratio further supported disulfidptosis induction. qPCR confirmed upregulation of four key disulfidptosis-related genes (ACTB, GYS1, SLC7A11, and MYH9) in response to HDM exposure. Moreover, HDM treatment triggered a pronounced pro-inflammatory response, as evidenced by the elevated mRNA expression of cytokines IL-25, IL-33, TSLP, IL-6, and IL-8.

Conclusion: Our findings reveal an association between disulfidptosis-related gene signatures and AD pathogenesis, suggesting that this pathway may contribute to the inflammatory response observed in lesional skin.

Background: Honey bee venom (HBV) often triggers severe IgE-mediated allergies. The major allergen icarapin (Api m 10) has attracted attention due to low occurrence in some HBV immunotherapy products. Despite being a major allergen, little is known about the Api m 10 structure and IgE-binding regions. This study aimed to characterize its IgE-binding epitopes and structure in more detail.

Methods: Overlapping Api m 10-specific peptides covering the sequences of the 11 known Api m 10-isoforms and variants were synthesized and spotted on microarray slides (15 amino acids (AA), off-set: 4 AA). Sera from 28 HBV-allergic patients with detectable Api m 10-specific IgE were used to characterize the distinct IgE-binding profiles to all Api m 10-variants. Sera from ten Api m 10-immunized BALB/c mice were used to investigate possible shared epitopes between humans and mice. All Api m 10-variants were investigated for secondary structural elements via circular dichroism spectroscopy and potential aggregation via dynamic light scattering.

Results: We identified 7 different linear IgE-binding motifs. All 28 patients' sera displayed IgE-binding to one specific area (present in Api m 10-isoforms 1 and 2 and putative splice variants 3, 4, 6), indicating a major IgE-epitope. IgE-inhibition provided evidence that the major epitope makes up less than 50% of the total IgE-binding capacity, suggesting that additional (most likely conformational) IgE-epitopes play an important role in Api m 10-sensitization. Api m 10-specific murine IgG and human IgE both predominantly bind to seven different AA-motifs, of which six are identical between both species. Api m 10-isoforms 1 and 2 displayed secondary structural elements and appeared to be aggregated.

Conclusion: The structural, clinical and preclinical insights into Api m 10 and its immunodominant epitopes gained in this study provide substantial insights for the future development of active and passive VIT as well as further treatment approaches.

Background: Hereditary angioedema (HAE) is a rare inherited disorder characterized by unpredictable and potentially life-threatening attacks of swelling. This international Delphi panel aimed to address questions related to on-demand treatment of HAE attacks.

Methods: A modified Delphi method was conducted with three rounds of surveys. Two non-voting co-chairs designed and managed the surveys, data collection, and analysis with a third-party administrator. The international panel consisted of 19 expert HAE clinicians. Consensus was defined as ≥ 75% agreement with ≥ 75% of panelists voting.

Results: The panel confirmed 24 statements across five key areas related to on-demand treatment: defining "early" treatment, barriers to early administration, burden of treatment, tolerability and convenience, and patient-clinician interactions. Panelists defined early treatment as ≤ 60 min after onset of an HAE attack. Obstacles to early treatment include recognition of an HAE attack, and embarrassment/anxiety about administering parenteral treatment. Access to on-demand treatment (i.e., carrying medication, cost, insurance coverage, regulatory approval) can be a burden for patients with HAE, and increasing access may improve adherence to guidelines. Logistical obstacles of parenteral administration that impact convenience, tolerability concerns (e.g., side effects), and cost of medication can all limit early use of on-demand treatment. Additional options for on-demand therapies beyond parenteral treatments could reduce some of the burdens. Panelists agreed that patient-physician shared decision-making should be utilized.

Conclusions: The Delphi consensus statements demonstrate the need for accessible and convenient on-demand treatments for HAE attacks that will enable patients with HAE to improve adherence to guidelines.

Allergic rhinitis (AR) and asthma caused by cat dander have a highly variable prevalence across countries, which can reach 30% of the population in some regions. Cat allergens are widely distributed in the environment, making exposure nearly unavoidable, even in non-cat-owning households. Eight cat allergens have been identified, with Fel d 1 and Fel d 4 being particularly associated with the development and severity of asthma. Symptoms can range from mild nasal and eye symptoms to severe asthma exacerbations, with many patients experiencing polysensitization to other allergens. Management usually begins with allergen avoidance and pharmacotherapy, but these approaches are often insufficient. Allergen immunotherapy (AIT), both sublingual (SLIT) and subcutaneous (SCIT), offers a disease-modifying strategy, though allergen potency, composition, standardization issues, and low prescription rates limit its use. AIT formulations that include allergens beyond Fel d 1, such as Fel d 4, show promise in improving cat-induced asthma and rhinitis outcomes. Additionally, novel approaches for antigen presentation or combination therapies with monoclonal antibodies may enhance the effectiveness and safety of AIT. To increase treatment success, personalized care using component-resolved diagnostics to identify sensitization profiles and better education for both physicians and patients are essential in the broader adoption of cat AIT.

Food allergy (FA) in early childhood can be challenging for families, even before a diagnosis is made, as parents often experience anxiety and have to change their routines. Research integrating parental and pediatrician perspectives during the pre-diagnostic phase is scarce. This study aimed to develop a journey map illustrating the FA pre-diagnostic process in early childhood from both perspectives. We triangulated 30 transcripts (16 parent interviews; 11 interviews and three focus groups with pediatricians) from two qualitative studies within the Food Allergy Biomarker Application Consortium (NAMIBIO App) using qualitative content analysis and data visualization. Four phases emerged: (non-)awareness, suspicion, healthcare seeking, and diagnostics. Parents were often unaware of FA risks, even with risk factors present. Pediatricians hesitated to address FA risk proactively, due to lacking specific guideline recommendations and concerns about triggering parental health-related anxiety. Both parents and pediatricians mentioned gaps in communication between pediatricians and midwives. During the suspicion phase, families searched for information or adjusted feeding practices while symptoms were often vague. Healthcare seeking often involved lengthy referrals. Pediatricians reported knowledge gaps among colleagues regarding FA. In the diagnostic phase, parents perceived delays in diagnosis; pediatricians mentioned limited resources, particularly for oral food challenges. Integrating both perspectives revealed shared concerns and different views on how to improve the process. Key intervention points to improve the pre-diagnostic process include clear, up-to-date guidelines, risk communication and improved interdisciplinary collaboration to reduce uncertainty and promote parental confidence.