International Archives of Allergy and Immunology最新文献

Introduction Breast cancer (BC) is a common cancer type in women and a major cause of death. CD300a is an inhibitory receptor expressed on immune cells, particularly mast cells (MCs). CD300a ligands expression was found on several cancer cells. We hypothesized that CD300a has a role in suppression of anti-tumor immunity in BC. Methods To test our hypothesis, we induced the 4T1 BC model in WT and CD300a-KO mice and evaluated, by toluidine blue staining, the activation level of tumor associated MCs. 4T1 cells were co-cultured with WT or CD300a-KO mouse bone marrow derived MCs (BMMCs) and 4T1 cell viability was analyzed using trypan blue. Human MDA-231 BC cells were co-cultured with cord blood derived MCs (hCBMCs) and soluble hCD300a-Fc was added. FACS analysis for MDA-231 cell viability and WB for CD300a signal transduction in CBMCs were performed. Results In vivo, smaller 4T1-cell tumors with more activated MCs were found in CD300a-KO mice. In vitro, 4T1 cell growth was reduced in co-culture with WT BMMCs and further reduced with CD300a-KO BMMCs. Similarly, growth of MDA-231 BC cells in co-culture with CBMCs was reduced following treatment with CD300a-Fc which feasibly interfered with CD300a pro-tumorigenic interactions. CD300a signal transduction pathway was activated in CBMCs co-cultured with MDA-231 cells and this activation was inhibited following treatment with CD300a-Fc. Conclusion Our results would imply that in BC, tumor cells activate CD300a on MCs and probably on other immune cells to downregulate their anti-tumorigenic activity and therefore suggest CD300a as a potential immune-suppressor in BC.

Objective: Asthma is a heterogeneous disease with varying clinical presentations. Hypogammaglobulinemia may increase susceptibility to respiratory tract infections and thereby influence asthma morbidity.

Subjects and methods: We retrospectively analyzed 332 children aged 4-12 years who were followed for asthma at a tertiary pediatric allergy and clinical immunology clinic between 2015 and 2020. Patients were categorized as normogammaglobulinemic (NGG) (n=286) or hypogammaglobulinemic (HGG) (n=46). Hypogammaglobulinemia was defined as persistently low IgG (below -2 SD for age), with or without concomitant low IgA and/or IgM.

Results: Children in the HGG group had an earlier onset of asthma symptoms and earlier asthma diagnosis, and lower breastfeeding rates (p<0.001, p=0.001, and p=0.024, respectively). The prevalence of atopic dermatitis and parental atopy was higher, and the annual frequency of upper respiratory tract infections, acute otitis media, lower respiratory tract infections (bronchopneumonia) not requiring hospitalization, and asthma exacerbations were significantly higher in this group (all p<0.005). Inhaled corticosteroid therapy was initiated and discontinued at younger ages among HGG children (p<0.001 and p=0.002, respectively). Atopic sensitization rates did not differ between groups.

Conclusion: In this tertiary-care cohort, HGG defined by persistently low IgG was associated with earlier-onset asthma symptoms and a higher infection and exacerbation burden. These findings may support considering immunologic evaluation and closer monitoring in a subset of children with asthma.

Introduction: Egg allergy restricts dietary diversity. Although oral immunotherapy (OIT) has demonstrated efficacy in treating egg allergy, this approach carries the risk of anaphylaxis. In the egg ladder (EL) approach, egg proteins are gradually introduced from extensively heated forms to less processed ones. Here, we aimed to compare the efficacy and safety of EL versus OIT in infants with egg allergy.

Methods: This single-center retrospective cohort study involved children aged <2 years who had been diagnosed with IgE-mediated egg allergy between 2014 and 2022. We utilized a historical cohort design comparing patients treated with OIT (2014-2018) with those treated with the EL approach (2018-2022). The study's primary outcomes were: (1) tolerance to whole egg (at least half of one whole egg) and (2) tolerance to egg-containing processed foods (ECPFs). Adverse events (AEs) were also assessed.

Results: A total of 163 children received OIT, whereas 89 underwent EL. Whole‑egg tolerance after 2 years of follow-up was similar between the groups (EL: 58% vs. OIT: 52%, P = 0.355). ECPF tolerance was higher with EL than with OIT (EL: 80% vs. OIT: 64%, P = 0.014). The overall AE rates were comparable between the approaches (EL: 28% vs. OIT: 34%, P = 0.397); however, treatment‑related anaphylaxis occurred only with OIT (three cases). Kaplan-Meier curves showed no difference in whole‑egg tolerance between the two approaches (P = 0.681), but the time to ECPF tolerance was shorter with EL (P = 0.009).

Conclusion: In this real-world cohort of infants with egg allergy, the EL approach achieved whole‑egg tolerance comparable to OIT and a substantially faster and higher tolerance to egg-containing processed foods, as expected given the EL protocol design. Although overall AE rates were similar between the approaches, no treatment‑related anaphylaxis occurred with EL, suggesting that the EL approach represents a safer and more practical strategy for dietary expansion in this age group.

Background: Cow's milk allergy (CMA) and egg allergy (EA) are among the most common food allergies in childhood. Although MMR vaccination is generally considered safe in food-allergic children, uncertainty persists among clinicians and families regarding the clinical relevance of residual food proteins in different MMR vaccine formulations. This study aimed to evaluate adverse reactions following administration of two different MMR vaccines in children with confirmed CMA and/or EA and to explore implications for safe immunization practices.

Methods: We retrospectively analyzed 140 children with diagnosed CMA and/or EA who received the MMR vaccine at our pediatric allergy clinic between September 2022 and May 2025. Demographic data, allergen-specific IgE levels, skin prick test results, MMR vaccine type and postvaccination reactions, were recorded. Two formulations were used: the Serum Institute of India vaccine (α-lactalbumin-containing) and Priorix® (α-lactalbumin-free).

Results: Among the patients, EA was observed in 60%, CMA in 17.1%, and both in 22.9%. Atopic dermatitis was present in 56.4%, urticaria in 31.4%, and a history of anaphylaxis in 12.1%. Overall, 57.9% (n=81) received the α-lactalbumin-containing vaccine, while 42.1% (n=59) received Priorix®. Only one patient (0.7%) experienced anaphylaxis after vaccination with the α-lactalbumin-containing formulation. No other serious adverse reactions were recorded.

Conclusion: MMR vaccination was generally well tolerated in children with egg and/or cow's milk allergy. While rare immediate reactions may occur with vaccines containing milk-derived proteins, these findings support continued adherence to current vaccination recommendations, with awareness of vaccine composition and appropriate vaccination settings rather than vaccine avoidance.

Background: Climate change has increased wildfires, air pollution, elevations in heat, and extreme weather events. While some negative effects on health are obvious, for example on pulmonary health, climate change's impact on rheumatic disease and autoimmune health may be less visible.

Summary: Multiple studies suggest that increased environmental heat is associated with gout flares and with hospitalizations for gout, likely worsens cardiovascular disease and increases biomarkers associated with inflammatory conditions. Increasing air pollution, including through smoke generated by wildfires or wildland urban interface fires, includes a mix of particulate matter (PM) and gases which can engender inflammation through oxidative stress. Studies discussed in the current paper suggest that smoke exposure may be associated with incident rheumatoid arthritis and systemic lupus erythematosus and with elevations in biomarkers associated with these and other diseases.

Key message: Understanding some of the potential health effects of exposure to wildfires and elevating heat, specifically increases in incidence of rheumatoid arthritis and systemic lupus erythematosus, disease activity, hospitalization risk, and disease biomarkers is important for clinicians, and represents an opportunity to educate their patients in the clinical setting and monitor them for health effects of climate change manifestations.

This retrospective study aimed to characterize the clinical features and diagnostic outcomes of selective aminopenicillin hypersensitivity among patients evaluated for β-lactam allergy between 2018 and 2024. A total of 1,340 patients were assessed, of whom 167 (12.5%) had confirmed selective allergy to aminopenicillins, predominantly affecting middle-aged women and presenting more frequently with immediate reactions such as urticaria/angioedema and anaphylaxis. All patients underwent a standardized work-up including skin prick and intradermal tests, patch tests and/or delayed intradermal testing when indicated, specific IgE measurement in immediate reactions, and drug challenge tests (DCT) with amoxicillin or amoxicillin-clavulanic acid. Intradermal testing and DCT were the most informative procedures, whereas specific IgE contributed minimally to the diagnosis of selective aminopenicillin allergy. Notably, all patients tolerated phenoxymethylpenicillin (penicillin V) during DCT, confirming selective sensitization to the aminopenicillin side chain and supporting the safe use of other β-lactams in this population. These findings highlight the clinical relevance of selective aminopenicillin allergy and underscore the importance of comprehensive diagnostic algorithms to optimize antibiotic stewardship and expand therapeutic options for labeled β-lactam-allergic patients.

Introduction: Early-life viral infections have been linked to both increased and a decreased risk for allergic disease later in life. Causative relationships have been difficult to prove and most likely both timing and type of infection(s) are of importance. The aim was to study the association between early-life viral infections and allergy at 20 years of age. In addition, to study how early viral infections are associated with other known risk factors for allergy.

Methods: A cohort of 281 individuals recruited before birth and categorized into three hereditary groups based on parental allergy status, defined by IgE-sensitized and allergic symptoms, was followed until age 20. Of these, 142 individuals completed both web-based questionnaires and clinical investigations. Infections were documented both as parent-reported between 0-2 years and seropositivity against 13 viruses at 2 years of age. Analyses included logistic regression and classification tree modeling.

Results: Individuals who experienced many respiratory viral infections (11-20) during their first two years of life had a higher prevalence of allergies compared to their peers with fewer than 10 respiratory viral infections; 58% vs, 34% (p=0.005). Cytomegalovirus (CMV) seropositivity at two years of age was associated with allergy at age 20 (p=0.026). As expected, parental allergy was also linked to the development of allergy.

Conclusion: Individuals who experienced frequent respiratory viral infections during early childhood, were seropositive for CMV by age two, and had two allergic parents, consistently developed allergic disease by age 20. Preventive strategies targeting early viral respiratory infections may help reduce future allergy.

Introduction In the lymphocyte transformation test (LTT) peripheral blood mononuclear cells (PBMCs) from patients with presumed drug allergy are cultured with the implicated drug. No systematic study has investigated how delayed processing or cryopreservation of PBMCs affects the sensitivity and specificity of the LTT to detect a drug sensitization. We evaluated the impact of delayed processing or cryopreservation of PBMCs on the sensitivity and specificity of the LTT focusing on interferon-y (IFN-γ) secretion as read-out. Additionally, we investigated the impact of the respective processing method on non-stimulated reference and TT-stimulated PBMCs. Methods Blood from 30 patients and 30 gender-matched controls was split for paired processing: one aliquot was processed immediately as internal reference of the patient/control, the other subjected to either a 24 h delay (n=15) or immediate processing followed by cryopreservation of the PBMCs (n=15). Thereby, each patient and control in the respective cohort served as its own reference for the assessment of the methodical processing impact. IFN-γ concentrations in PBMC culture supernatants were measured by ELISA. Results Cryopreservation of PBMCs resulted in a statistically non-significant trend towards higher sensitivity and specificity for detecting drug sensitization compared to delayed processing (45% vs. 31% and 81% vs 79%, respectively). 80% of the LTT results using cryopreserved PBMCs were consistent with those obtained from the immediately processed reference group. Conclusion When blood samples cannot be processed within 4 hours, cryopreservation of PBMCs appears preferable to delayed processing, as it better preserves LTT performance for detecting drug sensitization.

Introduction: Refractory allergic rhinitis (RAR) encompasses distinct immune-inflammatory endotypes, notably neurogenic and eosinophilic phenotypes, which may differentially respond to surgical intervention such as posterior nasal neurectomy (PNN). Identifying prognostic biomarkers to guide patient selection remains an unmet clinical need.

Methods: In this retrospective cohort study, 92 patients with moderate-to-severe RAR undergoing endoscopic PNN were stratified by 1-year outcome (effective: ≥50% improvement in Total Nasal Symptom Score [TNSS]). Preoperative serum levels of neuropeptides (Substance P, SP; Vasoactive Intestinal Peptide, VIP) were measured. Postoperative histopathological tissue eosinophil (TEos) counts (cells/HPF) from resected nasal mucosa were analyzed. Patients were categorized into Low-TEos (<10/HPF) and High-TEos (≥10/HPF) groups.

Results: The overall effective rate was 88.0%. The effective group exhibited significantly higher preoperative SP (56.4±12.1 vs. 38.2±9.5 pg/mL, P<0.001) and lower TEos counts (6.5±3.2 vs. 18.4±6.7 cells/HPF, P<0.001). Low TEos count strongly correlated with greater TNSS improvement (r=-0.62, P<0.001). Multivariate analysis identified High-TEos as an independent risk factor for poor outcome (OR=4.25, 95% CI: 1.56-11.58, P=0.005). ROC analysis confirmed TEos as a robust prognostic predictor (AUC=0.845, cutoff 11.5 cells/HPF).

Conclusion: High tissue eosinophilia defines an immune-endotypic subset of RAR with attenuated response to PNN, whereas a neurogenic-dominant profile (high SP, low TEos) predicts excellent surgical prognosis. TEos count serves as a clinically actionable histopathological prognostic biomarker, facilitating personalized surgical management through immune-endotype stratification.

Introduction: Real-world data are needed to improve our understanding of hereditary angioedema (HAE) management in different geographic regions. Here, we report outcomes of patients from Puerto Rico who received lanadelumab for HAE prophylaxis in the noninterventional EMPOWER Study (NCT03845400).

Methods: Eligible patients with HAE due to C1-inhibitor deficiency who initiated lanadelumab treatment were classified as newly treated or established on lanadelumab based on number of lanadelumab doses received before enrollment (<4 or ≥4, respectively). Lanadelumab exposure data were captured using electronic case report forms. Effectiveness was assessed by change in HAE attack rate before vs. after lanadelumab initiation. Safety was assessed through treatment-emergent adverse events (TEAEs).

Results: The Puerto Rican site enrolled 9 patients (1 newly treated who was lanadelumab-naïve, 8 established on lanadelumab). All patients were of Hispanic/Latino ethnicity (median [range] age: 55.0 [36-73] years; female: 77.8%). Eight out of 9 patients received lanadelumab 300 mg every 2 weeks; 1 patient established on lanadelumab received dosing every 4 weeks. Average lanadelumab exposure ranged from approximately 2.3 years to >2.5 years for patients newly treated and established on lanadelumab, respectively. In the newly treated patient, the physician-reported HAE attack rate decreased by 76% (1.99 vs. 0.47 attacks/month pre- vs. post-lanadelumab initiation); most physician-reported attacks were mild (16.7%) or moderate (58.3%). In patients established on lanadelumab, the mean (95% CI) physician-reported HAE attack rate was 0.26 (0.09-0.42) attacks/month; most physician-reported attacks were mild (25.7%) or moderate (56.8%). Real-world data on attack incidence reinforced the variability in presentation among patients; 2 were attack-free while on lanadelumab treatment. A total of 5 TEAEs were reported in 4 patients, none of which were serious or fatal. One patient experienced mild fatigue that was considered lanadelumab related.

Conclusion: Findings from this analysis support the clinical benefits and safety of lanadelumab treatment for HAE prophylaxis in patients from Puerto Rico.