German cockroach subcutaneous immunotherapy: Impact on nasal responses and allergen-specific immunity among urban children with asthma
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ABSTRACT:
PROVIDER: PRJNA1054571 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27287100.fastq.gz | Fastqsanger.gz | |||
| SRR27287200.fastq.gz | Fastqsanger.gz | |||
| SRR27287300.fastq.gz | Fastqsanger.gz | |||
| SRR27287101.fastq.gz | Fastqsanger.gz | |||
| SRR27287201.fastq.gz | Fastqsanger.gz |
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Project description:Background: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children.Objective: To determine if nasal allergen challenge (NAC) responses to cockroach allergen would improve following one year of SCIT.Methods: Urban children with asthma, cockroach-sensitized (skin prick test [SPT] and serum specific IgE) and reactive on NAC, participated in a yearlong randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean total nasal symptoms scores (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, SPT wheal size, serum allergen-specific antibody production and T-cell responses to cockroach allergen were assessed.Results: Changes in mean NAC TNSS did not differ between SCIT-assigned (n=28) versus placebo-assigned (n=29) participants (p=0.63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach sIgE decreased to a similar extent in both groups, while decreased cockroach SPT wheal size was greater among SCIT participants (p=0.04). A 200-fold increase in cockroach sIgG4 was observed among subjects receiving SCIT (p<0.001) but was unchanged in the placebo group. T-cell interleukin-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (p=0.002), while no effect was observed for interleukin-10 or interferon-gamma.Conclusion: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum sIgG4 production and down-modulation of allergen stimulated T-cell responses.
2024-12-18 | GSE250580 | GEO
Project description:Purpose: Next-generation transcriptome sequencing was done to understand host and eukaryotic microbiome changes in gene expression in association with defined insecticide selection pressures. The specific goal of this research was to understand whole-body physiological responses in German cockroaches and associated microbiota, at the metatranscriptome level, to defined insecticide selection pressures. Methods: We used the insecticide indoxacarb as the selecting insecticide, which is an important bait active ingredient for cockroach control. Six generations of selection with indoxacarb bait produced a strain with substantial (>20x) resistance relative to inbred control lines originating from the same parental stock. Results: Metatranscriptome sequencing revealed 1123 significantly differentially expressed genes in > two of three statistical models (81 upregulated and 1042 downregulated; FDR p<0.001; log2FC of +/- 1). The majority of upreglated genes were from the host cockroach while the majority of downregulated genes were from associated viruses and the eukaryotic microbiome. Conclusions: We show here significant impacts by insecticide selection on not only host stress-respnses like detoxification, but also on clearace of microbial parasites, pathogens, commensals and/or symbionts.
2021-12-07 | GSE188950 | GEO
Project description:Peripheral blood samples from children enrolled in the URECA cohort were collected at age 2. In short, at each URECA research center, within 16 hours of blood collection, mononuclear cells were separated and incubated (48 hours, 37C, 5% CO2) in the presence of German cockroach extract (10mg/mL; CR), dust mite extract (Dermatophagoides pteronyssinus, 10mg/mL; DM), tetanus toxoid (5mg/mL; TT), or medium alone (NS).
2018-03-27 | GSE96783 | GEO
Project description:Transcriptome responses to defined insecticide selection pressures in the German cockroach
| PRJNA780882 | ENA
Project description:This protocol outlines a single-site mechanistic study aiming to investigate long RNAs differentially expressed in the airway epithelium of asthma patients both at baseline and in response to segmental airway allergen challenges. Over approximately 14 days, the study spanned three visits: Visit 1: Comprehensive characterization of participants, encompassing lung function testing, methacholine challenge testing, and allergen skin prick testing. Visit 2: Participants underwent bronchoscopy wherein three procedures were performed a. Epithelial brushings were performed in a segmental airway (baseline sample) b. Diluent (inactive control) was instilled into another segmental airway c. A small dose of allergen was administered into a third segmental airway using standardized cat or dust mite allergen extracts. Visit 3 (24 hours or 7 days post Visit 2): Another bronchoscopy was carried out to collect epithelial brushings in the diluent challenged and allergen challenged segments The collected epithelial brush samples underwent analysis for mRNA expression in the epithelial brushings. The study successfully incorporated a total of 23 subjects, which included 18 asthmatics (with stable or well-controlled conditions), 2 allergic non-asthmatics, and 3 non-allergic non-asthmatics.
2024-03-08 | GSE250241 | GEO
Project description:PurposeCockroach feces are known to be rich in IgE-reactive components. Various protease allergens were identified by proteomic analysis of German cockroach fecal extract in a previous study. In this study, we characterized a novel allergen, a chymotrypsin-like serine protease.MethodsA cDNA sequence homologous to chymotrypsin was obtained by analysis of German cockroach expressed sequence tag (EST) clones. The recombinant chymotrypsins from the German cockroach and house dust mite (Der f 6) were expressed in Escherichia coli using the pEXP5NT/TOPO vector system, and their allergenicity was investigated by ELISA.ResultsThe deduced amino acid sequence of German cockroach chymotrypsin showed 32.7 to 43.1% identity with mite group 3 (trypsin) and group 6 (chymotrypsin) allergens. Sera from 8 of 28 German cockroach allergy subjects (28.6%) showed IgE binding to the recombinant protein. IgE binding to the recombinant cockroach chymotrypsin was inhibited by house dust mite chymotrypsin Der f 6, while it minimally inhibited the German cockroach whole body extract.ConclusionsA novel allergen homologous to chymotrypsin was identified from the German cockroach and was cross-reactive with Der f 6.
| S-EPMC4397369 | biostudies-literature
Project description:BackgroundNasal allergen challenge (NAC) could be a means to assess indication and/or an outcome of allergen-specific therapies, particularly for perennial allergens. NACs are not commonly conducted in children with asthma, and cockroach NACs are not well established. This study's objective was to identify a range of German cockroach extract doses that induce nasal symptoms and to assess the safety of cockroach NAC in children with asthma.MethodsTen adults (18-37 years) followed by 25 children (8-14 years) with well-controlled, persistent asthma and cockroach sensitization underwent NAC with diluent followed by up to 8 escalating doses of cockroach extract (0.00381-11.9 µg/mL Bla g 1). NAC outcome was determined by Total Nasal Symptom Score (TNSS) and/or sneeze score. Cockroach allergen-induced T-cell activation and IL-5 production were measured in peripheral blood mononuclear cells.Results67% (6/9) of adults and 68% (17/25) of children had a positive NAC at a median response dose of 0.120 µg/mL [IQR 0.0380-0.379 µg/mL] of Bla g 1. Additionally, three children responded to diluent alone and did not receive any cockroach extract. Overall, 32% (11/34) were positive with sneezes alone, 15% (5/34) with TNSS alone, and 21% (7/34) with both criteria. At baseline, NAC responders had higher cockroach-specific IgE (P = .03), lower cockroach-specific IgG/IgE ratios (children, P = .002), and increased cockroach-specific IL-5-producing T lymphocytes (P = .045). The NAC was well tolerated.ConclusionWe report the methodology of NAC development for children with persistent asthma and cockroach sensitization. This NAC could be considered a tool to confirm clinically relevant sensitization and to assess responses in therapeutic studies.
| S-EPMC8503840 | biostudies-literature
Project description:Asthma may be triggered by multiple mediators, including allergen-IgE cross-linking and non-IgE mechanisms. Several clinical studies have shown acute ethanol consumption exacerbates asthma, yet no animal model exists to study this process. We developed a model of ethanol-triggered asthma in allergen-sensitized mice to evaluate the mechanisms of ethanol inducing asthma-like responses. Outbred mice were exposed to cockroach allergens on Days 0 and 14; and on Day 21, mice received ethanol by oral gavage. Tracer studies confirmed alcohol aspiration did not occur. Within 30 minutes, alcohol induced degranulation of over 74% of mast cells, and multiple parameters of asthma-like pulmonary inflammation were triggered. Ethanol-gavaged mice had a fivefold increased production of eotaxin-2 (534 pg/mL) and a sevenfold increase in bronchoalveolar eosinophils (70,080 cells). Ethanol induced a 10-fold increase in IL-13, from 84 pg/mL in sensitized mice to 845 pg/mL in ethanol-gavaged sensitized mice. In cockroach allergen-sensitized mice, ethanol triggered asthma-like changes in respiratory physiology and a significant fivefold increase in airway mucin production. Importantly, none of these asthmatic exacerbations were observed in normal mice gavaged with ethanol. Cromolyn sodium effectively stabilized mast cells, yet increased mucin production and bronchoalveolar eosinophil recruitment. Together, these data show a single oral alcohol exposure will trigger asthma-like pulmonary inflammation in allergen-sensitized mice, providing a novel asthma model.
| S-EPMC3432429 | biostudies-literature
Project description:The role of gamma-delta T (γδT) cells in immune responses to common allergens is poorly understood. Here, we utilized single-cell (sc) transcriptomic analysis of allergen-reactive γδT cells in humans to characterize the transcriptional landscapes and TCR repertoires in response to cockroach (CR) and mouse (MO) allergens. Using a novel Activation-Induced Marker (AIM) assay that allows detection of γδT cells combined with scRNA sequencing and TCR repertoire analysis, we identified both shared and allergen-specific γδT cell activation patterns and gene expression profiles. While CR extract activated both Vδ1 and Vδ2 subsets, MO extract primarily stimulated Vδ2 cells. Our analysis revealed allergen-specific clusters with distinct functional signatures, including enhanced inflammatory responses and cytotoxic effector functions in MO-specific γδT cells and natural killer cell-mediated immunity and IFNγ signaling in CR-specific populations. Comparison of allergic and non-allergic individuals highlighted differences in gene expression and TCR repertoires, including a higher IFNG expression in the CR-allergic compared to non-allergic cohorts, suggesting that phenotypic and functional differences are associated with γδT allergen responses. This study provides insights into the cellular and molecular heterogeneity and functionality of allergen-reactive γδT cells, offering a foundation for understanding their role in allergic diseases and potential therapeutic interventions.
2025-04-10 | GSE294268 | GEO
Project description:BackgroundCockroach is an important allergen in inner-city asthma. The diagnosis and treatment of cockroach allergy has been impeded by the lack of standardized cockroach extracts.ObjectiveWe investigated the utility of a mediator release assay based on rat basophil leukemia (RBL) cells for comparing the potency of German cockroach extracts.MethodsRBL cells (line 2H3) transfected with human FcepsilonRI were passively sensitized with sera from subjects with cockroach allergy and stimulated with serial dilutions of 3 commercial cockroach extracts (1:10 weight/volume). In addition, the in-house prepared extract was tested in separate experiments with pooled sera that produced optimal performance in the RBL assay. N-hexosaminidase release (NHR) was used as a marker of RBL cell degranulation and was examined in relation to the intradermal skin test (ID(50)EAL) and serum cockroach-specific and total IgE levels.ResultsThe median cockroach-specific IgE concentration in 60 subjects was 0.72 kU(A)/L (interquartile range, 0.35-2.97 kU(A)/L); 19 sera (responders) produced a minimum 10% NHR to more than 1 extract. Responders had higher median cockroach-specific IgE (7.4 vs 1.0 kU(A)/L) and total IgE (429 vs 300 kU/L) levels than nonresponders. Ranking of extract potency was consistent between the mediator release assay and the ID(50)EAL. For the in-house prepared cockroach extract, the dose-response curves were shifted according to the concentration of the extract. NHR was reproducible between different experiments by using pooled sera.ConclusionThe mediator release assay measures biologic potency and correlates with the ID(50)EAL. It should be further evaluated to determine whether it could be used to replace intradermal skin test titration for assessing the potency of cockroach extract.
| S-EPMC2952833 | biostudies-literature