Search Results (187)

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

Background and Objectives: The average prevalence of sensitization to house dust mite in developed countries is more than 20%. The three major allergens of D. pteronyssinus—Der p 1, Der p 2, and Der p 23—have been associated with asthma severity. Allergen-specific immunotherapy (ASIT) is the only personalized and effective treatment that can change the natural course of allergic diseases such as allergic rhinitis or allergic asthma. Despite ASIT being an established treatment method, its effectiveness is still assessed using patient-reported outcome measures that determine quality of life, and there are no objective biomarkers that can accurately and reliably indicate the therapeutic efficacy of ASIT. This study aimed to monitor sensitization profiles to allergens, assess the effectiveness of ASIT, and evaluate total nasal symptom score (TNSS) and quality of life after six months of ASIT treatment. Materials and Methods: The molecular allergy diagnostic system was used to assess changes in patients’ sensitization profiles to allergens, and the validated questionnaires RQLQ and TNSS were used for quality-of-life assessment. Results: After 6 months of ASIT treatment against house dust mite allergens, a statistically significant increase in sIgE against the Der p 23 component was noted. In addition, a significant decrease in practical problems and an improvement in patients‘ emotional state were observed, while the TNSS score remained unchanged. Conclusions: Continuous monitoring of the Der p 23 component during further stages of ASIT is, therefore, essential to determine whether the observed changes reflect de novo sensitization or represent an immunological response to therapy. 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

Objective: Ongoing debates focus on the role of human leukocyte antigen (HLA) class II expression in shaping clinical phenotypes of chronic inflammatory airway diseases. This study seeks to clarify the impact of class II HLA on chronic obstructive pulmonary disease (COPD) and asthma–COPD overlap (ACO). Method: The expression levels of HLA-DQ/DR in blood immune cells were analyzed in 116 participants: 41 with COPD, 37 with ACO, 20 with pure asthma, and 18 healthy subjects (HS). Results: In the COPD group, HLA-DR protein expression levels were significantly elevated on blood M2a monocytes (7695 ± 3743 vs. 5391 ± 3153 MFI, p = 0.026), helper T cells (2551 ± 956 vs. 1836 ± 531 MFI, adjusted p = 0.018), cytotoxic T cells (1591 ± 531 vs. 1360 ± 477 MFI, adjusted p = 0.036), and B cells (20,667 ± 7985 vs. 15,694 ± 2003 MFI, adjusted p = 0.031) compared to the HS group. Conversely, no significant changes were observed in the asthma group. In ACO patients, helper T cells showed increased HLA-DR protein expression (2416 ± 914 MFI; adjusted p = 0.016) compared with the HS group. Higher levels of HLA-DR expression correlated with reduced pulmonary function, frequent exacerbations, and more severe symptoms. Following one year of treatment in 14 COPD and 16 ACO patients, HLA-DR protein expression on blood helper T cells, cytotoxic T cells, M2a monocytes, and neutrophils significantly declined (all p < 0.05). In vitro experiments demonstrated that exposure of M2- or M1-polarized THP-1 cells to a stimulus mix containing cigarette smoke extract, house dust mite antigens, and lipopolysaccharide led to up-regulation of HLA-DR expression. This response was linked to increased apoptosis and reduced production of reactive oxygen species. Conclusions: Up-regulation of HLA-DR in COPD and ACO patients may represent a novel biomarker for assessing disease severity and treatment response. Additionally, it could serve as a useful tool to distinguish COPD and ACO from asthma. Full article

Background/Objectives: To investigate the relationship between patient age and the clinical efficacy of subcutaneous immunotherapy (SCIT) for allergic rhinitis (AR), aiming to provide a reference for patient selection and efficacy improvement in clinical practice. Methods: We conducted a retrospective statistical analysis of clinical data from 240 AR patients who underwent standardized house dust mite (HDM) SCIT for at least 6 months at our hospital between 2019 and 2025. Patients were stratified into four age groups (children, young adults, middle-aged adults, and the elderly) according to the World Health Organization (WHO) classification. The clinical efficacy, nasal symptom scores, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, peripheral blood regulatory T cell (Treg) and regulatory B cell (Breg) levels, and adverse reactions were analyzed across these age strata. Additionally, to investigate the underlying mechanisms, we utilized a public single-cell transcriptomic dataset (GSE176269; n = 35, age 4 months-65 years) to assess the relationship between T cell senescence and age through data integration and senescence gene set scoring. For multiple comparisons, the significance level was adjusted using the Bonferroni method. This adjustment ensured the overall significance level (α) of the study was maintained at 0.05, and the final adjusted significance level (α′) for each age group was 0.0125. Results: The overall response rate for the entire cohort was 62.5%. Age-stratified analysis revealed a significantly higher response rate in children (83.3%) compared to middle-aged and elderly patients (48.5% and 20%, respectively), with the difference being statistically significant (p < 0.001). Following treatment, both total nasal symptom scores and RQLQ scores decreased significantly across all age groups compared to baseline (p < 0.001). Peripheral blood Treg and Breg levels increased post-treatment in all age groups; however, the increase was not statistically significant in the middle-aged and elderly groups (p > 0.0125). The incidence of systemic adverse reactions was 4.17% (all Grade I), occurring primarily in the child and young adult groups, but the difference among age groups was not statistically significant (p > 0.0125). Mechanistically, our single-cell analysis revealed that T cells within the nasal mucosa exhibit significant age-dependent senescence. Conclusions: SCIT is a safe and effective treatment for AR across all age groups. However, pediatric patients appear to derive greater benefit compared to middle-aged and elderly patients, a finding that corresponds with age-stratified immunological data. Therefore, different efficacy expectations should be considered when selecting SCIT for patients of varying ages, and future research should explore strategies targeting T cell senescence to enhance desensitization efficacy in elderly patients. Full article

Background/Objectives: The gut microbiome has an important role in immune regulation, and dietary interventions that support a balanced microbiota may help to prevent the development of allergic asthma. Dietary fibers can beneficially affect the intestinal microbiome, but due to the diversity of fiber types, the effects differ. In this study, we investigate the preventive effects of two mixes of short-chain and long-chain (1:1 and 9:1 ratio) fructo-oligosaccharides (FOS) in a mouse model of house dust mite (HDM)-induced allergic asthma. Methods: BALB/c mice received FOS-supplemented (1% w/w) diets before and during intranasal exposures to HDM. Endpoint airway hyperreactivity measurements were performed, followed by the collection of bronchoalveolar lavage fluid (BALF), lung, serum and cecum content. Fecal microbiome composition was determined by DNA sequencing and short-chain fatty acid (SCFA) levels were determined in the cecum, serum and lung. Results: Fecal microbiome analyses revealed an increased abundance of Prevotellaceae after FOS1:1 supplementation in HDM-allergic mice. Additionally, FOS1:1 protected against an HDM-induced increase in basal airway resistance. Both FOS1:1 and FOS9:1 restored the systemic acetate levels in HDM-allergic mice. The two FOS supplementations did not affect HDM-induced inflammatory cell influx in the BALF. However, FOS1:1 increased the frequency of Th1-cells and prevented an HDM-induced increase in the Th2/Th1 balance. Upon ex vivo restimulation with HDM, lung cell suspensions of FOS1:1-fed mice produced less type 2-related cytokines compared to control-supplemented mice, and FOS9:1 followed a similar pattern. Conclusions: Specific short-chain and long-chain FOS ratios differentially affect the microbiome and immune system in a mouse model with HDM-induced allergic airway inflammation. Dietary supplementation with FOS1:1 shifts the immune response away from type 2, suggesting that dietary fibers like FOS1:1 may contribute as a part of a broader strategy to modulate HDM-induced allergic asthma. Full article

Background/Objectives: Mechanical alloknesis (m-alloknesis), the sensation of itch evoked by normally non-pruritic mechanical stimuli, is commonly observed in dry skin-associated conditions, such as xerosis, atopic dermatitis (AD), and psoriasis. Janus kinase (JAK) inhibitors are currently used to treat AD and suppress inflammation and itch. However, their specific roles in the modulation of m-alloknesis remain unclear. Therefore, in this study, we investigated the effects of various oral JAK inhibitors on m-alloknesis using a murine model of AD. Methods: An AD-like phenotype was induced in mice through the repeated topical application of an ointment containing Dermatophagoides farinae (house dust mite) extract. The mice were then orally treated with one of three JAK inhibitors: the JAK1/2 inhibitor baricitinib, the JAK1-selective inhibitor abrocitinib, or the JAK2-selective inhibitor AZ960. M-alloknesis was evaluated by quantifying scratching behavior in response to 30 controlled mechanical stimuli applied to lesional skin. Results: The JAK inhibitor treatments did not affect skin barrier integrity, dermatitis severity, or spontaneous scratching behavior. However, baricitinib and abrocitinib significantly reduced m-alloknesis scores, whereas AZ960 had no effect. Conclusions: These results suggest that JAK1 signaling plays a critical role in the induction of m-alloknesis in AD. Selective JAK1 inhibition is a promising therapeutic strategy for attenuating m-alloknesis and improving quality of life for patients with AD, independent of general skin inflammation and barrier function. 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

Der p 23 induces a high-frequency sensitization in allergic individuals. However, its allergenic activity and clinical impact are scarce. We aimed to evaluate the ability of rDer p 23 to induce allergic inflammation in a mouse model and to test IgE reactivity in humans. Female Balb/c mice were sensitized and challenged with rDer p 23 and Dermatophagoides pteronyssinus extract. Specific antibodies were determined by ELISA, inflammatory cell infiltration and goblet cells hyperplasia were evaluated by lung histology, and bronchial hyperreactivity (BHR) was assessed by the FinePoint RC System^TM and whole-body plethysmography (WBP). IgE reactivity was evaluated by ELISA, the basophils activation test (BAT) and the skin pick test (SPT) in humans. rDer p 23, produced in Escherichia coli, adopts a random coil structure, predominantly exists in a monomeric state, and exhibits high stability. rDer p 23-treated mice showed a significant increase in lung resistance and bronchial hyperreactivity, as well as in eosinophils, neutrophils, and T cell count in bronchoalveolar lavage fluid (BALF). Cytokine and antibodies profiles were biased to a Type-2 response. No significant difference was observed in group 2 Innate Lymphoid Cells (ILC-2s) in lung and regulatory T cells (Treg) in the spleen. In asthmatic individuals sensitized to D. pteronyssinus, serum IgE reactivity to rDer p 23 was 67.5%. BAT and SPT results were significantly higher in allergic patients. Our findings support the pro-allergenic role of rDer p 23 in the development of the pathological features of asthma. 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

Between 1% and 2% of the world’s population is sensitised to mites. Aetiological diagnosis is key to the management of allergic patients. However, methods based solely on morphological criteria are ambiguous in many cases. Polymerase chain reaction of ribosomal genes represents a valuable complementary approach. The 5 most representative species (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Tyrophagus putrescentiae, Blomia tropicalis and Lepidoglyphus destructor) were selected as sources of allergens. They were first identified morphologically and the 18S rRNA gene sequences were obtained from the GenBank database. Alignment of the nucleotide sequences of the 18S rRNA ribosomal gene enabled the identification of the conserved and divergent regions in all of them. The alignment allowed the design of a pair of oligonucleotides in conserved regions of the gene, to amplify the sequence of interest in each of the species. We performed genomic DNA extraction, quantification and purity. PCR, using oligonucleotides designed to amplify the 18S sequence fragment of interest, showed the exact size for each species. Amplification, efficiency curves and melting points resulting from the amplification of the 18S amplicon of the five species were obtained. The oligonucleotides designed for real-time PCR studies, allow species identification by amplifying the specific fragment of each species using real-time PCR. Full article

Background/Objectives: In this study, we focused on a mixed microbial culture of Lactobacillus paracasei, Pichia membranifaciens, and Saccharomyces cerevisiae (LS) as a new probiotic and examined the therapeutic and preventive effects of topical treatment with LS in a mouse model of atopic dermatitis (AD). Methods: Immunomodulatory effects of LS were examined with murine dendritic cell lines (DC2.4) by measuring the interleukin (IL)-10 and tumor necrosis factor (TNF) α levels. The anti-inflammatory effects of LS were evaluated in stimulated human epidermal keratinocytes (HaCaTs) by focusing on the production of IL-8 and thymus and activation-regulated chemokine (TARC). Therapeutic and preventive properties of topical treatment with LS (10%) were finally examined in a mouse model of AD developed by topical sensitization to house dust mite ointment. Clinical symptoms, back skin thickness, and transepidermal water loss (TEWL) were monitored weekly, and the immune responses in the auricular lymph nodes were analyzed after necropsy. Results: LS treatment significantly enhanced the secretions of IL-10 and TNFα by DC2.4 cells. IL-8 and TARC production by stimulated HaCaT cells was significantly decreased by co-culturing with LS. Although there were no significant changes in clinical symptoms, skin thickness, or TEWL in the therapeutic setting of the AD mouse model, the number of IgE-positive B cells and IL-4 levels in the local lymph nodes significantly decreased in the LS treatment group. Preventive treatment with LS significantly decreased AD symptoms compared to those in AD control mice. Conclusions: Our findings indicate that the immunomodulatory and anti-inflammatory effects of LS prevent the development of AD. 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

Background: Early-life sensitization to house dust mites (HDMs) is a recognized risk factor for adverse respiratory allergic outcomes. Methods: We investigated the clinical characteristics of infants under two years of age who visited our allergy clinic for evaluation with detectable HDM-specific IgE (sIgE) and compared them to HDM-sIgE–negative infants. Results: Among 1793 infants tested for HDM sIgE, 96 (5.4%) demonstrated sensitization. In the HDM-positive cohort, the prevalence of atopic dermatitis was 74.0% (90.9% among those <12 months), food allergy was 57.3% (100% among those <12 months), egg white sensitization was 71.9% (90.9% among those <12 months), and cow’s milk sensitization was 56.3% (81.8% among those <12 months). Atopic dermatitis, food allergy, ≥4 wheezing episodes, physician-diagnosed asthma, allergic rhinitis, egg white sensitization, cow’s milk sensitization, and sensitization to three or more food allergens were significantly more common in the HDM-positive group compared with the HDM-negative group. Significant correlations were observed between HDM sIgE and total IgE levels, as well as between HDM sIgE and egg white sIgE levels. Overall, HDM sensitization in infants was most frequently accompanied by atopic dermatitis and egg white sensitization. Conclusions: These findings suggest that early HDM sensitization should be closely monitored, particularly in infants with atopic dermatitis and food allergies who exhibit elevated total IgE and egg white sIgE levels. Full article