Search Results (74)

Background/Objectives: Allergic rhinoconjunctivitis (AR) induced by house dust mites (HDMs) is a common condition that impairs quality of life, and allergen immunotherapy is the only treatment accepted to modify its natural course. However, real-world evidence on polymerized HDM subcutaneous immunotherapy (SCIT) remains limited. We evaluated the up to 24-month effectiveness of polymerized HDM SCIT and examined how baseline symptom burden affects the measured response. Methods: In a retrospective, single-arm, real-world cohort, 353 patients (mean age 15.9 (12.3) years) with HDM-induced AR with/without asthma (asthma subpopulation, n = 112) initiated polymerized SCIT (ALXOID^®, Inmunotek S.L., Spain) with an extract of house dust mites (Dermatophagoides pteronyssinus, D. farinae, Blomia tropicalis). Patients were followed for up to 24 months; 139 contributed an observation at month 12 and 67 at month 24. The primary outcome was the Rhinoconjunctivitis Combined Symptom–Medication Score (RCSMS); secondary outcomes were a visual analog scale (VAS) and the ESPRINT-15 quality-of-life questionnaire. Effectiveness was estimated using mixed models for repeated measures. The pre-specified primary-analysis population was restricted to a baseline RCSMS ≥ 2 to avoid floor effects and regression to the mean at low baseline scores. Results: At month 24, the RCSMS decreased by 0.938 points (−35.3%) in the full cohort and by 48.3% in the baseline RCSMS ≥ 2 population; in the full cohort, the VAS and ESPRINT-15 improved by 50.6% and 69.7%, respectively (all p < 0.001; within-subject effect sizes were small for the full-cohort RCSMS and medium for all other outcomes). The shape of the improvement trajectory did not differ by age group, and all age groups exceeded the minimal clinically important difference; the age analysis was exploratory. Patients with baseline RCSMS < 2 showed continued improvement in VAS and ESPRINT-15 scores. In contrast, the RCSMS increased, a pattern consistent with a statistical floor effect, suggesting limited responsiveness of the score at low baseline values. Conclusions: Up to 24 months, polymerized HDM SCIT was associated with clinically meaningful improvements in symptoms, medication use, and quality of life, most clearly in patients with a baseline RCSMS ≥ 2. Baseline symptom severity should be considered when interpreting combined symptom–medication outcomes in allergen immunotherapy. The single-arm design precludes causal inference. Full article

Background: Bronchial asthma is a chronic inflammatory airway disease characterized by acute bronchoconstriction and type 2-driven inflammation. This study investigated whether inhaled amitriptyline, a functional inhibitor of acid sphingomyelinase, exerts both bronchodilatory and immunomodulatory effects in experimental murine models of allergic airway inflammation (AAI) and human cellular systems. Methods: Acute AAI was induced in mice using ovalbumin (OVA) and house dust mite (HDM) protocols, respectively. Inhaled amitriptyline (3.3 mg/mL) was administered for either 20 days (short-term) or 36 days (long-term). Lung function was assessed using FlexiVent^®, and inflammatory markers including IgE, eosinophils, and type 2 cytokines were measured in bronchoalveolar lavage fluid and lung tissue. Complementary experiments were included using passively sensitized PCLSs and human type 2-differentiated CD4⁺ T cells. Results: Inhaled amitriptyline improved lung mechanics in both the OVA and HDM models, reducing total respiratory resistance and elastance. In the OVA model, eosinophil and T cell counts in BALF were decreased, whereas immunomodulatory effects were less pronounced in the short-term HDM model. In human T_H2 cells, no significant changes in cytokine production or gene expression were observed. Ex vivo, amitriptyline dose-dependently inhibited allergen-induced bronchoconstriction in PCLSs. Conclusions: Inhaled amitriptyline improves lung function across murine models of AAI, supporting its potential in exhibiting model-dependent immunomodulatory effects, and directly attenuates allergen-induced bronchoconstriction, supporting its potential as a bronchodilator with context-dependent immunomodulatory properties. Full article

Allergen-specific IgE multiplex serology enables the molecular characterization of sensitizations in large populations. To determine the sensitization prevalence and spectrum in dogs suspected of having allergies in the US, we analyzed results from 21,121 serum samples tested in 2024 and 2025 using the Pet Allergy Xplorer (PAX) 238-allergen platform. Sensitization to at least one allergen and to at least one environmental allergen was detected in 90.7% and 86.2% of dogs, respectively. House dust mites (HDMs) were the predominant allergens (79.5%), followed by Hymenoptera venoms (39.8%), meats (21.9%), weeds (21.5%), and tree pollens (18.6%). Sensitization to the Dermatophagoides farinae HDM was the most prevalent (76.7%). Unsupervised clustering of 16,366 sensitized dogs identified six biologically coherent profiles centered on flea saliva, mammalian serum albumins/IgGs, honeybee venom, HDM group-2 allergens, storage mites, and PR-10-family allergens. A second, pollen/plant-food-focused analysis found clusters associated with Parietaria Par j 2, ragweed, granule-bound starch synthases, and PR-10 allergens, as well as a minor Phl p 6-associated grass pollen profile. Altogether, these results define the molecular sensitization repertoire of dogs suspected of allergic diseases in the US and provide the background for interpreting IgE serological results and optimizing allergen selection for immunotherapy. Full article

House dust mites (HDMs) are major indoor allergens linked to asthma and atopic dermatitis, creating demand for safer, natural alternatives to synthetic acaricides and anti-allergy agents. This study aimed to investigate the dual bioactivity of curcuminoid extract from Curcuma longa to address HDM allergy through two distinct but complementary scopes: an environmental approach evaluating direct acaricidal efficacy to reduce allergen exposure and a cellular approach investigating the anti-inflammatory potential to mitigate the host’s underlying immune response. Curcuminoids were extracted using Soxhlet extraction with 70% ethanol and characterized via TLC, FTIR-ATR, and LC-MS. Acaricidal activity against HDMs was evaluated using extract-impregnated filter papers (0.1–10 mg/mL) over 24 h. Cytotoxicity and anti-inflammatory effects were assessed in HaCaT keratinocytes and RAW264.7 macrophages through cell viability, migration, phagocytic activity, nitric oxide (NO) inhibition, and gene expression assays. The curcuminoid extract demonstrated potent, dose-dependent acaricidal activity against HDM, achieving 100% mortality at 10 mg/mL within 24 h. A safe sub-cytotoxic concentration (≤0.001 µg/µL) preserved HaCaT cell migration and metabolic activity. In LPS-stimulated RAW264.7 cells, curcuminoids significantly reduced inflammatory NO production (p < 0.01) while enhancing phagocytic activity. Overall, these findings highlight curcuminoids as a sustainable natural strategy for reducing HDM exposure and mitigating allergic inflammation. Full article

Interleukin-22 binding protein (IL-22BP) is a soluble decoy receptor that competitively inhibits IL-22 by preventing its interaction with the IL-22 receptor. Although the IL-22 receptor is primarily expressed on non-hematopoietic cells, such as airway epithelial cells, the role of IL-22BP in the pathogenesis of asthma remains uncertain. We observed that IL-22BP was upregulated in the airways of wild-type (WT) mice intranasally sensitized and challenged with house dust mite (HDM) extract. To directly elucidate the function of IL-22BP in allergic airway responses, IL-22BP-deficient (IL-22BP−/−) and WT mice were sensitized and challenged with HDM, and airway responses were systematically assessed. IL-22BP−/− mice exhibited significantly lower airway hyperresponsiveness (AHR) compared to WT mice following sensitization and challenge with HDM. In contrast, eosinophil counts in bronchoalveolar lavage (BAL) fluid did not differ significantly between the two groups. Similarly, levels of interleukin (IL)-4, IL-5, IL-6, IL-13, IL-17A, and keratinocyte chemoattractant (KC) in BAL fluid were comparable between WT and IL-22BP−/− mice. Notably, IL-22 levels in lung homogenates were significantly higher in IL-22BP−/− mice than in WT mice after sensitization and challenge with HDM. These findings suggest that inhibition of IL-22BP attenuates the development of allergen-induced AHR, an effect likely mediated through enhanced IL-22 activity rather than alterations in airway inflammation or type 2 cytokine production. Full article

Atopic dermatitis (AD) is increasingly interpreted through frameworks emphasizing barrier dysfunction, type 2 cytokine signaling, pruritus pathways, and microbial dysbiosis, often relegating IgE-mediated mechanisms to secondary roles. In this narrative review, we synthesize historical, clinical, immunologic, and histopathologic evidence to propose a conceptual model in which IgE-bearing antigen-presenting cells (APCs)—including Langerhans cells, inflammatory dermal dendritic cells, and inflammatory dendritic epidermal cells (IDECs)—participate in an IgE-dependent amplification loop that may contribute to the chronicity of extrinsic (IgE-associated) AD. Evidence from human studies indicates that FcεRI-expressing APCs can acquire environmental allergens through IgE, enhancing antigen uptake and T-cell activation, while mast cells and basophils further reinforce type 2 inflammation through IgE-dependent and IgE-augmented pathways. Although these mechanisms have been described across distinct experimental and clinical contexts, their integration into a unified pathogenic circuit remains hypothesis-driven. We therefore present an interpretive framework that organizes these partially validated mechanisms into a coherent model linking cutaneous sensitization, allergen capture, APC activation, Th2 polarization, and spongiosis formation. This conceptual synthesis aims to reposition IgE-mediated processes within the broader pathophysiology of extrinsic AD and to highlight potential therapeutic implications for targeting IgE–FcεRI signaling and IgE-dependent APC biology. Full article

Background and Objectives: Dysfunction of the airway epithelial barrier is increasingly recognized as an early pathogenic mechanism in allergic respiratory diseases. Although individual aeroallergens such as ragweed (RW) pollen and house dust mite (HDM) are known to impair epithelial integrity, the effects of combined exposure, more reflective of real-world conditions, remain insufficiently characterized. This study aimed to evaluate the impact of single versus combined allergen exposure on airway epithelial barrier function using a multimodal experimental approach. Materials and Methods: Differentiated normal human bronchial epithelial (NHBE) cells were exposed to RW (100 µg/mL), HDM (100 µg/mL), or a combined extract (RW + HDM; total 100 µg/mL). Barrier function under air–liquid interface conditions was assessed by transepithelial electrical resistance (TEER), while real-time cellular responses were evaluated using xCELLigence impedance monitoring. Structural alterations were examined by occludin-based immunofluorescence imaging, and transcriptional changes associated with epithelial stress and inflammation were analyzed by RT-qPCR. Results: Allergen exposure induced time- and concentration-dependent impairment of epithelial barrier function. Combined exposure resulted in the most pronounced and sustained reduction in TEER and impedance measurements. These functional changes were accompanied by disruption of tight junction organization and coordinated transcriptional modulation of genes involved in inflammatory and stress responses. Conclusions: Combined exposure to RW and HDM extracts induced more severe and persistent epithelial barrier dysfunction than individual allergens. These findings support the role of the airway epithelium as a central regulator of allergic airway disease and highlight barrier disruption as an early pathogenic event. The multimodal framework applied in this study provides an integrated platform for investigating epithelial responses to complex environmental exposures. Full article

Background: House dust mites (HDM) are one of the significant indoor allergen sources which cause IgE-mediated responses in most of the allergic individuals. HDMs are found in human habitats worldwide and Der p 2 is one of the major clinically relevant HDM allergens involved in triggering allergic diseases. The recombinant production of Der p 2 in plant systems provides a cost-effective and viable platform for developing diagnostic kits and allergen-specific immunotherapy. Methods: The D. pteronyssinus Der p 2 allergen was transiently expressed in Nicotiana benthamiana and its immunogenicity was evaluated in mice. The Der p 2 coding sequence was cloned into a geminiviral plant expression vector and introduced into N. benthamiana leaves via Agrobacterium tumefaciens-mediated infiltration. Recombinant Der p 2 proteins were purified from the crude extracts and confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and Western blot. The immunogenicity of the plant-produced Der p 2 proteins was further evaluated by immunizing mice following a prime–boost immunization regimen, and Der p 2-specific antibody responses were assessed by ELISA. Results: Recombinant Der p 2 was successfully expressed and purified from N. benthamiana, and immunized mice developed high levels of Der p 2-specific IgG antibodies, with antibody titers increased after booster immunization. Conclusions: The results demonstrate that the transient expression of Der p 2 in plants is a feasible and effective strategy for producing immunologically active recombinant allergen proteins for diagnostic and potential clinical applications. Full article

Background: Pulmonary neuroendocrine cells (PNECs) are rare airway sensory cells implicated in amplifying allergic inflammation, yet due to their scarcity, the contribution of PNECs to the metabolic programs and responses of the airway epithelium remains poorly defined. Using a newly developed PNEC-enriched human airway epithelial model (ePNEC), we investigated the influence of PNECs on neuroendocrine and immune-modulatory metabolite production in response to the common aeroallergen of the house dust mite (HDM). Methods: Human bronchial epithelial cells (HBECs) and ePNEC cultures were differentiated at the air–liquid interface. Global untargeted metabolomics was performed to quantify metabolite abundance at baseline and following stimulation with HDMs. Differential expression, overlap significance, metabolite class enrichment, and pathway analyses were used to define PNEC-specific metabolic programs. Results: Principal component analysis (PCA) demonstrated strong baseline separation between ePNECs and HBECs, with HDMs inducing additional within-cell-type shifts. ePNECs displayed broader and more pronounced metabolite changes than HBECs. Baseline differences were largely preserved following allergen exposure, with significant overlap in both up- and down-regulated metabolites. ePNECs exhibited enriched neurotransmitter-linked metabolites—including serotonin, L-noradrenaline, dopamine, and histamine—at baseline and after HDM exposure. Amino acid–centered metabolism dominated the dataset, with enhanced histidine and tryptophan pathway activity in ePNECs. Pathway analysis revealed significant enrichment of phenylalanine, tyrosine, tryptophan, glutathione, and arginine–proline metabolism in ePNECs, whereas HBECs showed no significant pathway-level enrichment after HDM exposure. Conclusions: Human ePNECs engage a distinct, neuroactive metabolic program that is amplified upon HDM exposure. These findings provide a metabolic framework for how PNECs shape epithelial and neuroimmune responses to inhaled allergens. Full article

Background/Objectives: The aim of this study was to evaluate the tolerability and effectiveness of subcutaneous immunotherapy (SCIT) in allergic adults and children treated with a polymerized-glutaraldehyde undiluted mixture of house dust mites (HDMs) under routine clinical practice. Methods: This was an observational, ambispective, controlled, real-world, multicenter study including patients ≥ 5 years with allergic rhinitis (AR), due to Dermatophagoides sensitization. Patients who started AIT with a D. pteronyssinus/D. farinae extract and those who continued symptomatic treatment were included in the treatment (DP&DF) and untreated (UT) groups, respectively. We evaluated adverse reactions (ARs) and changes in effectiveness variables through changes in symptoms, disease control, medication use, and patient- and investigator-reported outcomes. Results: We included 130 patients in the DP&DF group, and 90 (69.2%) adults, 23 adolescents (17.7%), 17 (13.1%) children, and 94 patients in the UT group. Patients received treatment for a mean (SD) of 9.01 (3.1) months at the time of evaluation. Seven (5.4%) patients, all adults, reported eight ARs, five local and three systemic (mean rate of 0.62 ARs per 100 injections); all recovered, and epinephrine was not required. The proportion of patients reporting no rhinitis symptoms at follow-up significantly increased (+13.6%; p < 0.001). Rhinitis frequency, intensity, and control significantly improved overall and in specific age groups. Similarly, the proportion of patients reporting no asthma symptoms at follow-up significantly increased (+29.0%; p < 0.001). The use of all symptomatic medications significantly decreased, while the UT group showed no significant changes, except for worsened asthma classification and control in specific age groups. Both investigators and patients perceived a marked improvement in symptoms and medication use, with high satisfaction scores reported on the visual analogue scale. Conclusions: A subcutaneous allergen extract with a mixture of HDMs is safe and effective for allergic rhinitis and asthma in adults and children in the real-world setting. Full article

Allergen sensitization profiles are increasingly affected by environmental and climate changes. This study exemplifies fundamental differences in molecular IgE sensitization profiles in two nearby regions in Argentina with different climatic conditions (La Plata and Bahía Blanca). A cross-sectional study was conducted involving 155 patients with allergic symptoms from La Plata and Bahía Blanca (34.0 ± 11.2 years, female/male: 83/72). Serum samples were analyzed for IgE reactivity using a chip containing 101 micro-arrayed allergen molecules. Statistical analyses were performed to compare allergen-specific IgE levels, sensitization prevalences and reported symptoms. Patients from La Plata—with subtropical weather—showed a higher prevalence of IgE reactivity to house dust mite (HDM) allergens (Der p 23: 74%; Der p 1: 53% and Der p 2: 56%) and more frequently reported asthma (AS) symptoms (40% vs. 24%) than patients from Bahía Blanca. In contrast, patients from Bahía Blanca, with dry and windy weather, exhibited higher sensitization rates to pollen allergens, particularly Phl p 1 (49%) and Ole e 1 (22%) as well as to Alternaria alternata (Alt a 1, 35%) and reported a significantly higher prevalence of skin manifestations (54% vs. 31%) than those from La Plata. Cat allergen Fel d 1 was an equally important sensitizer in both regions (La Plata 30% and Bahía Blanca 37%). Sensitization to class 1 food allergens was rare in both groups (1–8%), including non-specific lipid transfer proteins (peanut Ara h 9 and peach Pru p 3) but IgE sensitizations to genuine peanut allergens were almost absent. Important regional differences in allergen sensitization profiles were observed between two geographically close regions with different climatic conditions. Our findings underscore the relevance of region-specific allergen profiling and highlight the clinical utility of molecular allergy diagnosis for a more precise allergen identification and improved management of allergic diseases. Full article

Given their nutritional features and environmental sustainability, black soldier fly (Hermetia illucens) larvae are currently being considered in Europe for commercialization as human food. The primary goal of this study is the determination of in vitro IgE-cross-reactivity to recombinant tropomyosin (_HITPM) and arginine kinase (_HIAK) of H. illucens in subjects sensitized to crustaceans and/or mites. Dot blot assays for recombinant _HITPM were carried out with the sera of 48 subjects, 30 sensitized to crustaceans (Cr+) and/or house dust mites (HDM+) (STUDY group) and 18 non-sensitized (CTRL group). A higher rate of IgE-reactivity to recombinant _HITPM was found in the STUDY group compared to non-sensitized controls (73% vs. 44%; p 0.066). No significant relationship was achieved upon dot blot assays for _HIAK. No relevant association between a positive history of food reactions and immunoreactivity to _HITPM and to _HIAK was reported (15% in _HITPM+ vs. 6% in _HITPM-, p NS; 28% in _HIAK+ vs. 50% in _HIAK-, p NS), contrary to the _HITPM+Cr+HDM+ subset (50% vs. 0%, p 0.022). Considering the wide overlap of pan-allergens within the Arthropoda phylum, concerns about allergenic potential due to the eventual consumption of H. illucens-enriched foods might be valid. Therefore, targeted studies involving basophil activation tests, skin prick tests, and a double-blind placebo-controlled oral food challenge using H. illucens are needed. Full article

Introduction: Apart from the typical AR phenotype and its standard clinical manifestations—rhinorrhea, sneezing, nasal itching, and congestion—the so-called local allergic rhinitis (LAR) can be observed in a subset of subjects presenting rhinitis symptoms, a negative skin prick test (SPT), and serum-specific immunoglobulin E (sIgE) for the relevant allergens and confirmed with a positive nasal provocation test (NPT), which is the gold standard in LAR diagnosis. Our study aims to assess the clinical symptoms and local mucosal sIgE presence induced by NPT and natural exposure to HDM allergens in subjects with suspected LAR. Methods: In total, 25 suspected LAR subjects were included in the study. The total nasal symptom score (TNSS) and visual analog scale (VAS) were used for the subjective assessment. A nasal provocation test (NPT) was performed with house dust mite allergens. The nasal lavage technique was used for nasal secretion acquisition, in which the levels of sIgE were measured. Results: During the period of increased exposure vs. the off-exposure period, the TNSS and VAS were significantly higher (p = 0.0361 and p = 0.0031, respectively). Levels of IgE specific to Dermatophagoides pteronyssinus in nasal lavage were high (p = 0.0502). Similarly, high levels of sIgE to Dermatophagoides farinae were noted (p = 0.0164). Comparing pre-NPT and post-NPT results, LAR diagnosis was confirmed in 8 subjects. Only the VAS score was higher after a positive NPT. Both sIgE to Dermatophagoides pteronyssinus and Dermatophagoides farinae in nasal lavage were higher after a positive NPT; however, the change was not statistically significant. A higher fold change in the median relative value (sIgE/Total IgE) for both allergens was noted in the positive-NPT group compared to the negative-NPT group. Conclusions: Assessing the local nasal production of sIgE and other inflammatory mediators may contribute to expanding our knowledge of LAR pathogenesis. Further studies including a larger number of subjects are needed for a better understanding of the LAR entity in terms of diagnosis and treatment options. Full article

Air–liquid interface (ALI) cultures offer a physiologically relevant in vitro model of the airway epithelium (AE), capable of recapitulating key structural and functional features observed in vivo. In this study, we established and validated a murine ALI culture system comprising pseudostratified epithelia with functional tight junctions, ciliated cells and goblet cells. To assess their innate immune functions, we designed and 3D-printed an autoclavable aerosol deposition chamber, which allowed us to expose differentiated AE cultures to house dust mite (HDM) allergen. Upon HDM exposure, AE cells mounted a time-dependent innate immune response characterized by the secretion of complement component C3, the generation of its active cleavage products C3a and increased expression of C3aR and C5aR1. This was associated with increased intracellular TSLP and IL-25 production and TSLP release in AE cells. Progressive loss of tight junction integrity and reduced transepithelial electrical resistance (TEER) demonstrated epithelial susceptibility to allergen protease-induced cell damage. Together, we established a murine ALI system preserving airway epithelial architecture and a nebulization system to study innate immune activation of AE cells in response to HDM mimicking the initial phase of allergen sensitization. More generally, we described a powerful and accessible platform for studying epithelial-driven mechanisms in murine airway immune responses. Full article

Background: Allergen immunotherapy (AIT) is generally considered a safe treatment modality, with systemic reactions (SRs) representing its most significant adverse events, despite their low incidence. This study aimed to evaluate the frequency and characteristics of SRs associated with subcutaneous allergen immunotherapy (SCIT) and to identify potential risk factors. Methods: We conducted a retrospective analysis of 47,982 SCIT injections administered to 317 patients over 468 SCIT courses between January 2019 and January 2024. The study population consisted of 26 patients diagnosed with allergic rhinitis sensitized to pollen and/or house dust mites (HDMs), as well as individuals with venom allergies who experienced SRs to SCIT during the study period. Data collected included demographic characteristics, presence of asthma, allergen sensitivities, immunoglobulin E (IgE)-related immunologic biomarkers, and adverse reactions. SRs were classified according to the World Allergy Organization (WAO) SCIT SR Grading System. Results: A total of 26 SCIT-related SRs were documented in 26 patients (57.7% female; mean age 37.3 ± 10.04 years), corresponding to an incidence rate of 0.05% per injection, and 8.2% per patient. Asthma was present in 42.3% of patients. Prior adverse reactions to SCIT were noted in eight patients (30.8%). SRs occurred during the build-up phase in 61.5% of cases, compared with the maintenance phase. In 46.2% of patients, a single allergen was administered, while 53.8% received multiple allergens. Based on the WAO grading system, 30.8% of SRs were classified as grade 1, 42.3% as grade 2, 15.4% as grade 3, and 11.5% as grade 4. No fatalities were reported. The majority of SRs were early onset (88.5%), and epinephrine was administered in 76.9% of the cases. A higher serum specific IgE to total IgE (sIgE/tIgE) ratio was significantly associated with more severe SRs. Conversely, a history of prior allergic reactions to SCIT appeared to correlate with milder SRs. Conclusions: Our findings confirm that SRs to SCIT are rare, and severe reactions are infrequent. A higher serum sIgE/tIgE ratio can be risk factor for severe SRs. Nonetheless, a thorough risk–benefit assessment is essential prior to initiating SCIT, particularly in patients with identified risk factors. Full article