Mite-specific IgE Levels Research Articles

T-cell receptor diversity and allergen sensitivity in childhood asthma and atopic dermatitis.

Childhood allergies of asthma and atopic dermatitis (AD) involve an overactive T-cell immune response triggered by allergens. However, the impact of T-cell receptor (TCR) repertoires on allergen sensitization and their role in mediating different phenotypes of asthma and AD in early childhood remains unclear. A total of 78 children, comprising 26 with asthma alone, 26 with AD alone, and 26 healthy controls (HC), were enrolled. TCR repertoire profiles were determined using a unique molecular identifier system for next-generation sequencing. Integrative analyses of their associations with allergen-specific IgE levels and allergies were performed. The diversity in TCR alpha variable region (TRAV) genes of TCR repertoires and complementarity determining region 3 (CDR3) clonality in TRAV/TRBV (beta) genes were significantly higher in children with AD compared with those with asthma and HC (p < .05). Compared with HC, the expression of TRAV13-1 and TRAV4 genes was significantly higher in both asthma and AD (p < .05), with a significant positive correlation with mite-specific IgE levels (p < .01). In contrast, TRBV7-9 gene expression was significantly lower in both asthma and AD (p < .01), with this gene showing a significant negative correlation with mite-specific IgE levels (p < .01). Furthermore, significantly higher TRAV8-3 gene expression, positively correlated with food-specific IgE levels, was found in children with AD compared with those with asthma (p < .05). Integrated TCR repertoires analysis provides clinical insights into the diverse TCR genes linked to antigen specificity, offering potential for precision immunotherapy in childhood allergies.

Incidence and causative agent distribution of viral-induced paediatric asthma exacerbations under strict infection control measures: a single-centre retrospective study in Japan

BackgroundThe prevalence of respiratory viruses in children changed under strict infection control measures during the coronavirus disease 2019 (COVID-19) outbreak. In this study, we investigated the frequency of viral detection in the nasopharynx of paediatric patients with asthma exacerbations requiring hospitalization during the COVID-19 pandemic, as well as the distribution of causative viruses.MethodsWe included paediatric patients admitted for asthma exacerbations between November 2020 and December 2022 at a single centre in Kobe, Japan. Demographic, clinical, and laboratory data were collected from their medical records and using additional questionnaires. All patients enrolled in this study met the diagnostic criteria for asthma exacerbations outlined in the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2020. Statistical differences were calculated using univariate analyses (chi-square or Mann‒Whitney U test).ResultsWe enrolled 203 children hospitalized for asthma attacks and collected nasopharyngeal samples from 189 patients. The median patient age was 3.0 years. Asthma severity was classified as mild (4.0%), moderate (82.3%), or severe (13.8%). The proportion of viral respiratory infections was 95.2% (180/189). The rate of patients with multiple viral infections was 20.6% (39/189). The most frequently detected pathogens were rhinovirus and enterovirus (RV/EV) at 69.3% (131/189), allowing for duplicate detection, followed by respiratory syncytial virus (RSV) at 28.6% (54/189). We also detected RV/EV almost every month compared to RSV and other viruses. In addition, RV/EV-positive patients were significantly older (p = 0.033), exhibited higher WBC counts (p < 0.001) and higher Eos counts (p < 0.001), had elevated total IgE levels (p < 0.001) and house dust mite-specific IgE levels (p = 0.019), had a shorter duration of hospitalization (p < 0.001), and had a shorter duration of oxygen therapy (p < 0.001). In patients positive for RV/EV, the use of ICSs significantly reduced the severity of the condition (p < 0.001).ConclusionEven under strict infection control measures, respiratory viruses were detected in the nasopharynx of almost all paediatric patients who had asthma exacerbations requiring hospitalization.

Higher House Dust Mite-Specific IgE Levels among Chronic Spontaneous Urticaria Patients May Implicate Higher Basophil Reactivity

Introduction: Allergen-specific IgE (sIgE) sensitization exists in a considerable fraction of chronic spontaneous urticaria (CSU) patients. Basophils have been implicated in the pathogenesis of CSU. This paper aimed to explore the relationship between allergic sensitization and basophil reactivity in CSU and the possible underlying mechanism. Methods: Basophil-enriched leukocytes were isolated from the peripheral blood of 76 CSU patients and 9 healthy controls. Basophil CD63 and FcεRIα (the alpha subunit of the high-affinity IgE receptor) expression in the blood samples with various house dust mite (HDM)-sIgE levels were determined by flow cytometry. Basophil reactivity and SHIP-1 (a molecule related to the IgE/FcεRI signaling pathway) expression were analyzed after stimulation with an HDM allergen or other stimuli. Results: HDM-sIgEstrong positive (≥3.5 kU/L) CSU patients had a significantly higher mean percentage of basophil CD63 and higher baseline levels of FcεRIα expressed by basophils than HDM-sIgEnormal (<0.35 kU/L) CSU patients and healthy controls; the same went for total serum IgE. After stimulation with Dermatophagoides pteronyssinus peptidase 1 (Derp1) alone or together with Derp1-sIgE, the stimulation index of CD63 and levels of FcεRIα expressed by basophils in HDM-sIgEstrong positive CSU patients were significantly higher than those in HDM-sIgEnormal CSU patients and healthy controls. Significantly more SHIP-1 mRNA expression in HDM-sIgEstrong positive CSU patients was induced after the combined stimulation in comparison to other subjects. Conclusion: CSU patients with higher HDM-sIgE levels (≥3.5 kU/L) may have higher CD63 and FcεRIα expression on peripheral blood basophils. Peripheral blood basophils in these CSU patients are more responsive to HDM allergen stimulation. Higher HDM-sIgE levels among CSU patients may implicate higher basophil reactivity.

Increased circulating T follicular helper 13 subset correlates with high IgE levels in pediatric allergic asthma.

We found an elevation of circulating TFH13 cell subset in asthmatic children and the frequency of TFH13 cells positively correlated with the plasma dust mite-specific IgE levels. These results indicated that TFH13 cell subset may be responsible for the immunopathogenesis of excessive IgE accumulation in children with allergic asthma.

Decrease in CD38+ TH2A cell frequencies following immunotherapy with house dust mite tablet correlates with humoral responses.

In line with evidence for a role of pathogenic TH2A in seasonal allergies, we previously showed that individuals suffering from food allergy exhibited a decrease in circulating TH2A cells following multi-food immunotherapy. Herein, we aim to confirm the decline of TH2A cells in individuals undergoing house dust mite immunotherapy (HDM-AIT) and extend our observation to a new subset of CD38 expressing activated TH2A cells. The frequencies of TH2A and CD38+ TH2A cells were analysed by flow cytometry in blood cells from 182 Japanese HDM-allergic individuals included in a 1-year clinical trial assessing the efficacy of HDM tablets. Interrelationship between these cellular responses and humoral mite-specific IgE and IgG4 levels was further explored. A decrease in TH2A cells was observed in both active and placebo groups. Interestingly, CD38+ TH2A cell frequencies significantly decreased only in active groups. In younger individuals (16-30years), both TH2A and CD38+ TH2A cells were significantly reduced in active groups but not in the placebo group. Significant inverse correlations were observed in the course of HDM-AIT between changes in TH2A or CD38+ TH2A frequencies and IgG4 antibody levels. We confirm the value of monitoring TH2A cell frequencies in allergic individuals and extend this observation to perennial allergy to HDM. We highlight the interest of CD38 to better identify the subset of TH2A cell down-regulated by AIT. Finally, correlated cellular and humoral responses observed in immunoreactive individuals stress that coordinated pathways occur in the adaptive responses during AIT.

Cross-talk between airway and gut microbiome links to IgE responses to house dust mites in childhood airway allergies

A connection between airway and gut microbiota related to allergen exposure in childhood allergies was not well addressed. We aimed to identify the microbiota alterations in the airway and gut related to mite-specific IgE responses in young children with airway allergies. This study enrolled 60 children, including 38 mite-sensitized children (20 rhinitis and 18 asthma), and 22 non-mite-sensitized healthy controls. Microbiome composition analysis of the throat swab and stool samples was performed using bacterial 16S rRNA sequencing. An integrative analysis of the airway and stool microbial profiling associated with IgE reactions in childhood allergic rhinitis and asthma was examined. The Chao1 and Shannon indices in the airway were significantly lower than those in the stool. Additionally, an inverse association of the airway microbial diversity with house dust mite (HDM) sensitization and allergic airway diseases was noted. Fecal IgE levels were positively correlated with the serum Dermatophagoides pteronyssinus- and Dermatophagoides farinae-specific IgE levels. Airway Leptotrichia spp. related to asthma were strongly correlated with fecal Dorea and Ruminococcus spp., which were inversely associated with fecal IgE levels and risk of allergic rhinitis. Moreover, four airway genera, Campylobacter, Selenomonas, Tannerella, and Atopobium, were negatively correlated with both serum mite-specific and fecal IgE levels. Among them, the airway Selenomonas and Atopobium spp. were positively correlated with stool Blautia and Dorea spp. related to asthma and allergic rhinitis, respectively. In conclusion, airway microbial dysbiosis in response to HDM and its cross-talk with the gut microbial community is related to allergic airway diseases in early childhood.

Asthma and allergic rhinitis risk depends on house dust mite specific IgE levels in PARIS birth cohort children

BackgroundThe natural history of allergic sensitization in childhood, and its impact on allergic disease development, needs to be clarified. This study aims to identify allergic sensitization and morbidity patterns during the first 8 years of life. MethodsThe study was conducted in the on-going population-based prospective Pollution and Asthma Risk: an Infant Study (PARIS) birth cohort. Sensitization profiles were identified by k-means clustering based upon allergen-specific IgE levels measured at 18 months and 8/9 years. Allergic morbidity profiles were identified by latent class analysis based on symptoms, symptom severity, treatments, and lifetime doctor-diagnoses of asthma, allergic rhinitis, and atopic dermatitis and on lower respiratory infections before 2 years. ResultsFive sensitization and 5 allergic morbidity patterns were established in 714 children. Children not sensitized or with isolated and low allergen-specific sensitization were grouped together (76.8%). A profile of early and transient sensitization to foods that increased the risk of asthma later in childhood was identified (4.9%). Children strongly sensitized (≥3.5 kUA/L) to house dust mite at 8/9 years (9.0%) had the highest risk of asthma and allergic rhinitis. Finally, timothy grass pollen at 8/9 years sensitization profile (5.3%) was related to respiratory allergic diseases, as was early onset and persistent sensitization profile (4.1%), this latter being also strongly associated with atopic dermatitis. Conclusions & Clinical RelevanceWe show that accurate assessment of the risk of allergic disease should rely on earliness and multiplicity of sensitization, involved allergens, and allergen-specific IgE levels, and not considering solely allergic sensitization as a dichotomous variable (allergen-specific IgE ≥0.35 kUA/L), as usually done. This is particularly striking for house dust mite. We are hopeful that, pending further confirmation in other populations, our findings will improve clinical practice as part of an approach to allergic disease prevention.

Gut microbial-derived butyrate is inversely associated with IgE responses to allergens in childhood asthma.

A comprehensive metabolomics-based approach to address the impact of specific gut microbiota on allergen sensitization for childhood rhinitis and asthma is still lacking. Eighty-five children with rhinitis (n=27) and with asthma (n=34) and healthy controls (n=24) were enrolled. Fecal metabolomic analysis with 1 H-nuclear magnetic resonance (NMR) spectroscopy and microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen-specific IgE levels for allergic rhinitis and asthma was also assessed. Amino acid, β-alanine, and butanoate were the predominant metabolic pathways in the gut. Among them, amino acid metabolism was negatively correlated with the phylum Firmicutes, which was significantly reduced in children with rhinitis and asthma. Levels of histidine and butyrate metabolites were significantly reduced in children with rhinitis (P=0.029) and asthma (P=0.009), respectively. In children with asthma, a reduction in butyrate-producing bacteria, including Faecalibacterium and Roseburia spp., and an increase in Clostridium spp. were negatively correlated with fecal amino acids and butyrate, respectively (P<0.01). Increased Escherichia spp. accompanied by increased β-alanine and 4-hydroxybutyrate appeared to reduce butyrate production. Low fecal butyrate was significantly associated with increased total serum and mite allergen-specific IgE levels in children with asthma (P<0.05). A reduced fecal butyrate is associated with increased mite-specific IgE levels and the risk of asthma in early childhood. Fecal β-alanine could be a specific biomarker connecting the metabolic dysbiosis of gut microbiota, Clostridium and Escherichia spp., in childhood asthma.

Thymol attenuates the worsening of atopic dermatitis induced by Staphylococcus aureus membrane vesicles

Staphylococcus aureus membrane vesicles (MVs) aggravate atopic dermatitis (AD) through the delivery of bacterial effector molecules to host cells and the stimulation of inflammatory responses. This study investigated the inhibitory effect of thymol, a phenolic monoterpene found in essential oils derived from plants, on the worsening of AD induced by S. aureus MVs both in vitro and in vivo. The sub-minimal inhibitory concentrations of thymol disrupted S. aureus MVs. Intact S. aureus MVs induced the expression of pro-inflammatory cytokine (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α) and chemokine (IL-8 and monocyte chemoattractant protein-1) genes in cultured keratinocytes, whereas thymol-treated S. aureus MVs did not stimulate the expression of these genes. Topical application of thymol-treated S. aureus MVs or treatment with thymol after intact S. aureus MVs to AD-like skin lesions diminished the pathology of AD. This included decreases in epidermal/dermal thickness and infiltration of eosinophils/mast cells, and inhibited expression of pro-inflammatory cytokine and chemokine genes in mouse AD model. Moreover, thymol significantly suppressed the Th1, Th2, and Th17-mediated inflammatory responses in AD-like skin lesions induced by S. aureus MVs, and reduced the serum levels of immunoglobulin (Ig) G2a, mite-specific IgE, and total IgE. In summary, thymol disrupts S. aureus MVs and suppresses inflammatory responses in AD-like skin lesions aggravated by S. aureus MVs. Our results suggest that thymol is a possible candidate for the management of AD aggravation induced by S. aureus colonization or infection in the lesions.

Cell Penetrating Peptide Derived from Human Eosinophil Cationic Protein Decreases Airway Allergic Inflammation

Cell penetrating peptide derived from human eosinophil cationic protein (CPPecp) is a 10-amino-acid peptide containing a core heparan sulfate (HS)-binding motif of human eosinophil cationic protein (ECP). It binds and penetrates bronchial epithelial cells without cytotoxic effects. Here we investigated airway-protective effects of CPPecp in BEAS-2B cell line and mite-induced airway allergic inflammation in BALB/c mice. In BEAS-2B cell, CPPecp decreases ECP-induced eotaxin mRNA expression. CPPecp also decreases eotaxin secretion and p-STAT6 activation induced by ECP, as well as by IL-4. In vivo studies showed CPPecp decreased mite-induced airway inflammation in terms of eosinophil and neutrophil count in broncho-alveolar lavage fluid, peri-bronchiolar and alveolar pathology scores, cytokine production in lung protein extract including interleukin (IL)-5, IL-13, IL-17A/F, eotaxin; and pause enhancement from methacholine stimulation. CPPecp treated groups also showed lower serum mite-specific IgE level. In this study, we have demonstrated the in vitro and in vivo anti-asthma effects of CPPecp.

Potential preventive effects of proactive therapy on sensitization in moderate to severe childhood atopic dermatitis: A randomized, investigator-blinded, controlled study.

Proactive therapy for atopic dermatitis (AD) effectively prevents exacerbation. However, its role in preventing subsequent sensitization to allergens has not been prospectively studied. We investigated whether proactive therapy for AD can effectively impact immunological parameters in a randomized, investigator-blinded, parallel group study. Thirty patients aged 3 months to 7 years with moderate to severe AD who had undergone an AD educational program were allocated to a proactive treatment group or a reactive treatment group. During the disease control period, patients in the proactive group performed intermittent preventive application of topical corticosteroid for 1 year. Changes in the severity scoring, quality of life measures and immunological parameters (serum thymus and activation regulated chemokine [TARC], total immunoglobulin E [IgE] and house dust mite-specific IgE levels) were evaluated and compared between the proactive and reactive treatment groups. Although the average topical corticosteroid ointment use per day in both groups was not significantly different, the severity and quality of life scores were significantly lower in the proactive group than in the reactive group at the final visit. In addition, compared with baseline levels, serum TARC levels remained significantly lower during proactive therapy, while house dust mite-specific IgE levels were significantly increased only in the reactive group. The results suggest that in addition to controlling the severity of AD, intermittent preventive administration of topical corticosteroids may prevent an increase in aeroallergen-specific IgE levels in patients with childhood AD. The use of TARC levels as a biomarker for AD remission is also supported.

Alpha‐tryptase gene variation is associated with levels of circulating IgE and lung function in asthma

summaryBackgroundTryptase, a major secretory product of human mast cells has been implicated as a key mediator of allergic inflammation. Genetic variation in the tryptases is extensive, and α-tryptase, an allelic variant of the more extensively studied β-tryptase, is absent in substantial numbers of the general population. The degree to which α-tryptase expression may be associated with asthma has not been studied. We have investigated the α-tryptase gene copy number variation and its potential associations with phenotypes of asthma.ObjectivesCaucasian families (n = 341) with at least two asthmatic siblings (n = 1350) were genotyped for the α-tryptase alleles, using high-resolution melting assays. Standards for the possible α-/β-tryptase ratios were constructed by cloning α-and β-tryptase PCR products to generate artificial templates. Association analysis of asthma affection status and related phenotypes [total and allergen-specific serum IgE, bronchial hyperresponsiveness to methacholine, forced expiratory volume in 1s (FEV1) and atopy and asthma severity scores] was undertaken using family-based association tests (FBAT).ResultsFour consistent melting patterns for the α-tryptase genotype were identified with alleles carrying null, one or two copies of the α-tryptase allele. Possessing one copy of α-tryptase was significantly associated with lower serum levels of total and dust mite-specific IgE levels and higher FEV1 measurements, while two copies were related to higher serum concentrations of total and dust mite-specific IgE and greater atopy severity scores.Conclusions and Clinical RelevanceAssociations of α-tryptase copy number with serum IgE levels, atopy scores and bronchial function may reflect roles for tryptases in regulating IgE production and other processes in asthma.

Topical application of Taglisodog-eum inhibits the development of experimental atopic dermatitis

Aim of studyTaglisodog-eum (▪, Tuo Li Xiao Du Yin), a standardized herbal formula, has been widely used to modulate diverse carbuncles in oriental medicine. However, it is still unclear whether Taglisodog-eum (TSE) can exert a beneficial role in dermatological disease. In this study, we examined the effect of topical application of TSE on experimental atopic dermatitis (AD) and elucidated its action mechanism. Materials and methodsTo test the effect of TSE treatment on IgE production in vitro, U266B1 cells and primary CD19+ B cells isolated from AD-induced mice were treated with TSE under LPS/IL-4 stimulation and then IgE level in the culture supernatant was measured by ELISA. To evaluate the effect of TSE treatment on the production of AD related pathogenic cytokines, CD4+ T cells isolated from AD-induced mice were treated with TSE under PMA/ionomycin stimulation, then the level of cytokine expression was analyzed by quantitative RT-PCR and ELISA. The effects of TSE on the NFκB promoter activity in T cells and on the expression level of Aicda (activation-induced cytidine deaminase) in B cells were examined. To further examine the in vivo efficacy of TSE on AD progression, TSE was topically applied to ears of mice with atopic dermatitis induced by painting of DNCB and house dust mite extract. AD Progression was estimated by following criteria: (a) ear thickness, clinical score, (b) serum total IgE and mite specific IgE level by ELISA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total ear cells and draining lymph node CD4+ T cells by quantitative real time PCR and ELISA. ResultsTreatment of TSE to the U266B1 cell line and primary CD19+ B cells isolated from AD-induced mice inhibited IgE production. Treatment of TSE down-regulated the expression of several cytokines (IL-4, IL-10, IL-13, IL-17, TNF-α and IFN-γ) in CD4+ T cells isolated from AD-induced mice. Topical application of TSE on the ears of AD-induced mice decreased the severity and progression of disease by reducing ear thickness, clinical scores including dryness, edema. TSE treatment reduced the infiltration of lymphocytes to the inflamed site analyzed by histological evaluation. TSE treatment also decreased serum IgE level and expression of AD-associated pathogenic cytokines (IL-4, IL-5 and IL-13) in total ear cells and dLN CD4+ T cells by inhibiting the translocation of NFκB into nucleus. ConclusionsOur study indicates that protective effect of Taglisodog-eum (TSE) in experimental atopic dermatitis is mediated by inhibiting IgE production and the levels of Th2 type cytokines, suggesting the beneficial effect of TSE on modulating atopic dermatitis.

Immunomodulatory effect of water soluble extract separated from mycelium of Phellinus linteus on experimental atopic dermatitis

BackgroundComplementary and alternative medicine (CAM) is becoming a popular treatment for modulating diverse immune disorders. Phellinus linteus (P. linteus) as one of the CAMs has been used to modulate cancers, inflammation and allergic activities. However, little evidence has been shown about its underlying mechanism of action by which it exerts a beneficial role in dermatological disease in vivo. In this study, we examined the immunomodulatory effects of P. linteus on experimental atopic dermatitis (AD) and elucidated its action mechanism.MethodsThe immunomodulatory effect of total extract of P. linteus on IgE production by human myeloma U266B1 cells was measured by ELISA. To further identify the effective components, P. linteus was fractionated into methanol soluble, water soluble and boiling water soluble extracts. Each extract was treated to U266B1 cells and primary B cells to compare their inhibitory effects on IgE secretion. To test the in vivo efficacy, experimental atopic dermatitis (AD) was established by alternative treatment of DNCB and house dust mite extract into BALB/c mice. Water soluble extract of P. linteus (WA) or ceramide as a positive control were topically applied to ears of atopic mouse every day for 2 weeks and progression of the disease was estimated by the following criteria: (a) ear thickness, clinical score, (b) serum total IgE, IgG and mite specific IgE level by ELSIA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total ear cells and CD4+ T cells by real time PCR and ELSIA.ResultsTreatment of total extracts of P. linteus to U266B1 inhibited IgE secretion. Among the diverse extracts of P. linteus, water soluble extract of P. linteus (WA) significantly reduced the IgE production in primary B cells and B cell line U266B1. Moreover, treatment of WA reduced AD symptoms such as ear swelling, erythema, and dryness and decreased recruitment of lymphocyte into the inflamed site. Interestingly WA treatment significantly reduced IgE level without affecting IgG levels and also down-regulated the levels of pathogenic cytokines (IL-4, IL-13, IL-12 and IFN-γ) and chemokines (CCL17 and CCL22) involved in AD development.ConclusionsOur study indicates that protective effect of water soluble extract of P. linteus in atopic dermatitis is mediated by inhibiting IgE production and expression of AD associated pathogenic cytokines as well as chemokines, suggesting the beneficial effect of P. linteus to modulate allergic skin disease.

Flaky Tail Mouse Denotes Human Atopic Dermatitis in the Steady State and by Topical Application with Dermatophagoides pteronyssinus Extract

The barrier abnormality, a loss-of-function mutation in the gene encoding filaggrin (FLG), which is linked to the incidence of atopic dermatitis (AD), is a recently discovered but important factor in the pathogenesis of AD. Flaky tail (Flg(ft)) mice, essentially deficient in filaggrin, have been used to investigate the role of filaggrin on AD. However, the relevancy of Flg(ft) mice to human AD needs to be determined further. In this study, we observed the clinical manifestations of Flg(ft) mice in the steady state and their cutaneous immune responses against external stimuli, favoring human AD. Under specific pathogen-free conditions, the majority of Flg(ft) mice developed clinical and histological eczematous skin lesions similar to human AD with outside-to-inside skin barrier dysfunction evaluated by newly devised methods. In addition, cutaneous hapten-induced contact hypersensitivity as a model of acquired immune response and a mite extract-induced dermatitis model physiologically relevant to a human AD were enhanced in Flg(ft) mice. These results suggest that the Flg(ft) mouse genotype has potential as an animal model of AD corresponding with filaggrin mutation in human AD.

A Six-SNP Haplotype of ADAM33 Is Associated with Asthma in a Population of Cartagena, Colombia

Background: A disintegrin and metalloprotein-33 (ADAM33) participates in the bronchial remodeling process in asthma, and genetic analyses pointed it out as a candidate gene in asthma. Methods: To analyze the association between ADAM33 and asthma and total and mite-specific IgE levels in a population of the Caribbean Coast of Colombia, we genotyped 6 single-nucleotide polymorphisms of ADAM33 in 429 asthmatics, 401 controls and 116 family trios using fluorogenic probes. Total and specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus were determined by ELISA. Case-control and family-based analyses were performed. Case-control association analyses were corrected by population stratification using a set of 52 ancestry-informative markers. Results: Eight common haplotypes were identified; among them, H4 (GCAGGG) was associated with asthma in the family group (Z score: –2.049, p = 0.04). We also found an association between the TT genotype of ST+7 and asthma in the case-control study (p = 0.05) that disappeared after correcting for multiple testing. In the family-based analysis, this genotype was a risk factor for asthma (p = 0.01), high total IgE (Z score: 2.546, p = 0.01) and high specific IgE against B. tropicalis (p = 0.02) and D. pteronyssinus (Z score: 2.414, p = 0.01). V4 was associated with specific IgE against B. tropicalis (p = 0.03); T2 with asthma (p = 0.03), high total IgE (p = 0.02) and IgE against D. pteronyssinus (p = 0.03) and T1 with high total IgE (p = 0.04). None of these associations was maintained after correction for multiple testing. Conclusions: Our findings suggest a relevant role of ADAM33 in thepathogenesis of asthma in this population.

Association of G‐protein‐coupled receptor 154 with asthma and total IgE in a population of the Caribbean coast of Colombia

G protein-coupled receptor 154 was described as an asthma susceptibility gene by positional cloning. It has been subsequently associated with asthma and other inflammatory diseases in several populations with different ethnic origin. Replication of associations adds reliability to these findings. To analyze the association of G protein-coupled receptor 154 with asthma and total and mite-specific IgE levels in a population of the Caribbean Coast of Colombia. We genotyped seven single nucleotide proteins (SNPs) in GPR154 in 475 asthmatics, 394 controls and 116 families from Cartagena, Colombia using either SnaPshot or TaqMan. Total and specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus were determined by ELISA. Hardy-Weinberg equilibrium was assessed and case-control and family-based analyses were performed to evaluate the association between the SNPs and their haplotypes and asthma and IgE. Association analyses in the case-control dataset were corrected by population stratification using 52 ancestry informative markers. Allelic distribution was similar to that described in other populations. Two SNPs were associated with the same direction of the effect in both datasets. Allele A of Hopo546333 was protective for asthma (case-control OR: 0.42; 95% CI: 0.17-0.99, P=0.042; P=0.043; families Z score=-2,236; P=0.025). Similarly, allele C of rs740347 conferred low risk for asthma (OR: 0.44; 95% CI: 0.28-0.70, P=0.00017; Pc=0.00037) and total IgE (OR: 0.29; 95% CI: 0.09-0.88, P=0.015; Pc=0.030) in the case-control study and families (Z score=-3.207, P=0.0013; Z score=-3.182, P=0.0014, respectively). Haplotype CCAGGT was associated with total IgE (OR: 1.76; 95% CI: 1.14-2.71, P=0.006, Pc=0.007) in the case-controls group and CGCGGT with both phenotypes (P=0.044 and P=0.032, respectively) in families. Neither SNPs nor haplotypes were associated with levels of mite-specific IgE. Our findings in a sample of asthmatics from Colombia suggest a relevant role of G protein-coupled receptor 154 in the pathogenesis of asthma and allergy.

Association of Mite-Specific IgE Level with Th2-Shifted Response of Peripheral Blood Mononuclear Cells to Stimulation with Mite Allergen and Airway Hyperresponsiveness in Children Sensitized to Mite

RATIONALE: IgE antibody response to dust mite provides a possible explanation for the higher total IgE levels and may help to explain the increased prevalence and severity of asthma. This study was designed to determine whether the serum level of mite-specific IgE is related to Th2 cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with mite allergen and airway hyperresponsiveness (AHR) in children sensitized to dust mite.

Normal Variation of Bronchial Reactivity in Nonasthmatics is Associated with the Level of Mite-Specific IgE

Objective. To investigate association between non-specific bronchial reactivity (NBR) and level of mite specific IgE amongst mite-sensitized non-asthmatic subjects. Methods. Subjects attending occupational check-up were assessed for: respiratory symptoms, atopic status (skin prick testing [SPT], total and specific IgE), spirometry and NBR. Individuals without history of respiratory disease (N = 234) were included into analysis. Results. All subjects had normal spirometry and 99% had normal NBR while 41.8% had detectable specific IgE to mites. Lung function parameters and NBR were significantly lower in mite sensitized subjects. Multiple regression analysis controlling for age, gender, smoking, family history, SPT, IgE, and lung function showed that NBR was significantly associated only with mite specific IgE level (ß = 0.26; 95% CI, 0.05–0.47; p = 0.018). Conclusion. Even in subjects without allergic symptoms, IgE-mediated sensitization does not appear to be all or nothing phenomenon influencing the normal variability of underlying airway reactivity.

Cat and dust mite allergen levels, specific IgG and IgG 4, and respiratory symptoms in adults

Exposure to allergen may induce a modified T(H)2 response characterized by high IgG(4) levels, absence of IgE sensitization, and a decreased risk of allergic respiratory symptoms. To assess the association of IgG(4) level with allergic respiratory symptoms in a community-based sample of adults. Information on exposure to cats, respiratory symptoms, and mattress allergen levels was obtained from 2780 adults. Levels of cat and house dust mite (HDM) specific IgE, IgG, and IgG(4) were measured. The association of exposure to allergen with IgG(4) and of IgG(4) with symptoms was assessed. Geometric mean (GM) cat specific IgG and IgG(4) was higher in subjects who had a cat that was allowed in the bedroom than in subjects without a cat (adjusted ratio of GM IgG(4), 1.41; 95% CI, 1.25-1.57). Levels of HDM specific IgG and IgG(4) were similar in subjects with undetectable and high (>20.22 microg/g) mattress Der 1 levels (adjusted ratio of GM IgG(4), 1.02; 95% CI, 0.89-1.17). There was no evidence that high cat or HDM specific IgG(4) levels were associated with less IgE sensitization or with fewer symptoms. In this community-based sample of adults, high IgG(4) levels to cat or HDM were not associated with a lower risk of allergic respiratory symptoms. In adults, high cat allergen exposure does not protect against respiratory symptoms.