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ACS Nano Aug 2023It has been shown that inhalation exposure to copper oxide nanoparticles (CuO NPs) results in pulmonary inflammation. However, immunomodulatory consequences after CuO NP...
It has been shown that inhalation exposure to copper oxide nanoparticles (CuO NPs) results in pulmonary inflammation. However, immunomodulatory consequences after CuO NP inhalation exposure have been less explored. We tested the effect of CuO NP aerosols on immune responses in healthy, house dust mite (HDM) asthmatic, or allergen immunotherapy (AIT)-treated asthmatic mice (BALB/c, females). The AIT consisted of a vaccine comprising HDM allergens and CpG-loaded nanoparticles (CpG NPs). AIT treatment involved mice being immunized (via subcutaneous (sc) injection; 2 doses) while concomitantly being exposed to CuO NP aerosols (over a 2 week period), starting on the day of the first vaccination. Mice were then sensitized twice by sc injection and subsequently challenged with HDM extract 10 times by intranasal instillation. The asthmatic model followed the same timeline except that no immunizations were administered. All mice were necropsied 24 h after the end of the HDM challenge. CuO NP-exposed healthy mice showed a significant decrease in T1 and T2 cells, and an elevation in T-bet Treg cells, even 40 days after the last exposure to CuO NPs. Similarly, the CuO NP-exposed HDM asthma model demonstrated decreased T2 responses and increased T-bet Treg cells. Conversely, CuO NP inhalation exposure to AIT-treated asthmatic mice resulted in an increase in T2 cells. In conclusion, immunomodulatory effects of inhalation exposure to CuO NPs are dependent on immune conditions prior to exposure.
Topics: Female; Mice; Animals; Copper; Inhalation Exposure; Asthma; Pyroglyphidae; Immunity; Nanoparticles; Oxides
PubMed: 37463491
DOI: 10.1021/acsnano.3c01668 -
Respiratory Research Jul 2023Accumulating clinical evidence links Obstructive Sleep Apnea (OSA) with worse outcomes of asthma, but impact on airway function remains sparsely studied. We tested...
INTRODUCTION
Accumulating clinical evidence links Obstructive Sleep Apnea (OSA) with worse outcomes of asthma, but impact on airway function remains sparsely studied. We tested effects of Chronic Intermittent Hypoxia (CIH) - a hallmark of OSA - on airway hyperresponsiveness (AHR), in a rat model of chronic allergen-induced inflammation.
METHODS
Brown Norway rats were exposed to six weeks of CIH or normoxia (NORM) concurrent with weekly house dust mites (HDM) or saline (SAL) challenges. At endpoint, we assessed responses to seven Methacholine (Mch) doses (0, 4, 8, 16, 32, 64, 128 mg/mL) on a FlexiVent system (Scireq). Maximal (or plateau) responses (reactivity) for total respiratory system Resistance (R) and Elastance (E), Newtonian airway resistance (R a measure of central airways function) and tissue damping (G, a measure of distal airways function) were plotted.
RESULTS
HDM/CIH-treated animals demonstrated the highest reactivity to Mch in R and E compared to all other groups (HDM/NORM, SAL/CIH and SAL/NORM p < 0.05 for all comparisons, for doses 5-7 for R, and for doses 4-7 for E). The enhanced R response was due to an increase in G (doses 4-7, p < 0.05 for comparisons to all other groups), whereas R was not affected by CIH.
CONCLUSIONS
In rats chronically challenged with HDM, concurrent CIH exposure induces AHR primarily in the distal airways, which affects the respiratory system frequency-dependent elastic properties.
Topics: Rats; Animals; Pyroglyphidae; Allergens; Respiratory Hypersensitivity; Lung; Hypoxia; Methacholine Chloride; Inflammation; Sleep Apnea, Obstructive; Disease Models, Animal
PubMed: 37468919
DOI: 10.1186/s12931-023-02493-4 -
Frontiers in Immunology 2023The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving...
Circulating T follicular helper 2 cells, T follicular regulatory cells and regulatory B cells are effective biomarkers for predicting the response to house dust mite sublingual immunotherapy in patients with allergic respiratory diseases.
The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4 cTfh cells were significantly decreased and the percentage of IFN-γ cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR.
Topics: Animals; Humans; Pyroglyphidae; Sublingual Immunotherapy; B-Lymphocytes, Regulatory; Asthma; Respiration Disorders; Dermatophagoides pteronyssinus; T-Lymphocytes, Regulatory; Biomarkers; T Follicular Helper Cells
PubMed: 38111589
DOI: 10.3389/fimmu.2023.1284205 -
Medicine Jan 2024To explore the relationship between specific immunoglobulin E levels in response to prevalent pollen and food allergens among patients suffering from localized allergic...
BACKGROUND
To explore the relationship between specific immunoglobulin E levels in response to prevalent pollen and food allergens among patients suffering from localized allergic diseases in the Dongying area of China, and to analyze the interconnectivity among these factors.
METHODS
This research encompassed allergic patients who visited the Allergy Department of Shengli Oilfield Central Hospital from January 2022 to January 2023. We examined the specific immunoglobulin E levels in the blood of 230 patients utilizing the Fobock platform provided by Jiangsu Haoeubo Company. Statistical analysis was conducted with SPSS 25.0 statistical software. The chi-square test evaluated the relevance of differences in gender and age. A value of P < .05 was considered statistically significant.
RESULTS
In this study, eggs emerged as the allergen with the highest number of sensitized individuals, closely followed by dust mite. Conversely, the least sensitized allergen was the cypress tree, closely followed by mango. Notably, male patients exhibited higher sensitivities to cottonwood (P < .05) and egg (P < .001) compared to female patients. Children aged 0 to 10 years showed increased sensitivity to variety of allergens. A significant correlation was observed among different allergens. The top ten allergen pairs with the highest correlation included Birch Tree and Cottonwood (0.88, P < .001), Cottonwood and Pine Tree (0.86, P < .001), Birch Tree and Pine Tree (0.84, P < .001), Pine Tree and Paulownia (0.81, P < .001), Dust Mite and House Dust Mite (0.76, P < .001), Birch Tree and Paulownia (0.73, P < .001), Cashew and Pistachio (0.71, P < .001), Apple and Hazelnut (0.71, P < .001), Cottonwood and Paulownia (0.71, P < .001), and Pine Tree and Ordinary Ragweed (0.70, P < .001).
CONCLUSION
This research sheds light on the patterns of allergen sensitization in Dongying, Shandong, highlighting that egg is the most prevalent sensitizing allergen. A notably high correlation was observed between Birch Tree and Cottonwood. This study enhanced the understanding of allergic diseases, explored the causes and mechanisms of allergies, strengthened the management of allergic diseases. Furthermore, it offers valuable insights for the clinical diagnosis and prevention of allergic diseases.
Topics: Child; Animals; Humans; Allergens; Food Hypersensitivity; Epidemiologic Studies; Pyroglyphidae; Betula; China; Immunoglobulin E
PubMed: 38241586
DOI: 10.1097/MD.0000000000036862 -
The Journal of Allergy and Clinical... May 2024House dust mite (HDM) is the most common allergen trigger globally for allergic rhinitis and atopic asthma.
Accurate determination of house dust mite sensitization in asthma and allergic rhinitis through cytometric detection of Der p 1 and Der p 2 binding on basophils (CytoBas).
BACKGROUND
House dust mite (HDM) is the most common allergen trigger globally for allergic rhinitis and atopic asthma.
OBJECTIVES
To expedite accurate confirmation of allergen sensitization, we designed fluorescent allergen tetramers to directly stain specific IgE on basophils to detect specific allergen sensitization using the flow cytometric CytoBas assay.
METHODS
Recombinant proteins of major HDM allergens (component), Der f 1, Der p 1, and Der p 2 were biotinylated and conjugated with fluorochrome streptavidins as tetramers. Blood samples from 64 patients who are HDM-allergic and 26 controls that are non-HDM-sensitized were incubated with allergen tetramers for evaluation of basophil binding (CytoBas) and activation (BAT) with flow cytometry.
RESULTS
The tetramers effectively bound and activated basophils from patients who are allergic but not from controls who are nonsensitized. CytoBas with Der p 1 as a single allergen had comparable sensitivity and specificity (92% and 100%) to BAT (91% and 100%) in detecting allergen sensitization, as did CytoBas with Der p 2 (95% and 96%) to BAT (95% and 87%). A positive staining for Der p 1 and/or Der p 2 in CytoBas was 100% sensitive and 96% specific for HDM allergy.
CONCLUSIONS
CytoBas has diagnostic accuracy for group 1 and group 2 HDM allergens that is comparable to BAT, but with additional advantages of multiple allergen components in a single tube and no requirement for in vitro basophil activation. These findings endorse a single, multiplex CytoBas assay for accurate and component-resolved diagnosis of aeroallergen sensitization in patients with allergic asthma and/or rhinitis.
Topics: Humans; Antigens, Dermatophagoides; Arthropod Proteins; Basophils; Cysteine Endopeptidases; Animals; Rhinitis, Allergic; Asthma; Female; Adult; Flow Cytometry; Male; Pyroglyphidae; Middle Aged; Adolescent; Young Adult; Immunoglobulin E; Allergens; Sensitivity and Specificity; Child
PubMed: 38360181
DOI: 10.1016/j.jaci.2024.02.002 -
Scientific Reports Aug 2023Cyclophilins (CyPs) are involved in basic cellular functions and a wide variety of pathophysiological processes. Many CyPs have been identified as the aetiological agent...
Cyclophilins (CyPs) are involved in basic cellular functions and a wide variety of pathophysiological processes. Many CyPs have been identified as the aetiological agent and influence on the immune system. In the present study, the physicochemical and immunologic characteristics of three proteins of CyPs family (CyPA, CyPB and CyPE) were analyzed. The results indicated that CyPE showed a closer evolutionary relationship with allergenic CyPA. The structure and antigenicity of CyPE was significantly similar with CyPA. B-cell epitopes of CyPE and CyPA were predicted via multiple immunoinformatics tools. Three consensus B-cell epitopes of CyPE and CyPAs were finally determined. To verify results of in silico analysis, three proteins of CyPs family (CyPA, CyPE and CyPB) were cloned and expressed from Dermatophagoides pteronyssinus. ELISA results indicated that the positive reaction rates of the three proteins to patient serum are CyPA (21.4%), CyPE (7.1%), and CyPB (0%), illustrating that the IgE activity was exhibited in CypA and CypE excluding CyPB. Structure and immunoinformatics analysis demonstrated that the RNA-binding motif of CyPE could reduce the immunogenicity of PPIase domain of CyPE. The reason that CyPB has no IgE activity might be the structure mutation of CyPB on B-cell epitopes.
Topics: Humans; Animals; Cyclophilins; Dermatophagoides pteronyssinus; Epitopes, B-Lymphocyte; Biological Evolution; Consensus
PubMed: 37604978
DOI: 10.1038/s41598-023-40720-6 -
Hong Kong Medical Journal = Xianggang... Oct 2023
Topics: Humans; Animals; Hypersensitivity; Allergens; Pyroglyphidae; Immunotherapy
PubMed: 37749053
DOI: 10.12809/hkmj2310696 -
The Journal of Allergy and Clinical... Jun 2024Allergic rhinitis with or without conjunctivitis can negatively impact many aspects of quality of life (QoL). The efficacy and safety of standardized quality (SQ)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Allergic rhinitis with or without conjunctivitis can negatively impact many aspects of quality of life (QoL). The efficacy and safety of standardized quality (SQ) sublingual immunotherapy (SLIT) tablets have been confirmed across large clinical trials in adults with grass, tree, ragweed, and house dust mite (HDM) allergic rhinitis with or without conjunctivitis.
OBJECTIVE
This pooled analysis investigates whether the reduction in symptom burden found across the clinical trials is supported by improvements in QoL.
METHODS
A total of 11 phase II/III randomized placebo-controlled trials across the SQ grass, tree, ragweed, and HDM SLIT tablets (grass: N = 3179; ragweed: N = 767; tree: N = 634; HDM: N = 2221) were included. QoL was assessed using the standardized Rhinitis Quality of Life Questionnaire (RQLQ), with the exception of 3 grass trials, which used the nonstandardized version. The overall RQLQ scores were expressed as a mean of 7 domains. In the pooled analysis, treatment was used as fixed effect; and the trial, and the interaction between region/country and trial as random effects.
RESULTS
The pooled analysis showed consistent and statistically significant improvements in overall RQLQ scores across all 4 SQ SLIT tablets versus placebo (pooled estimate [95% CI], P value-grass: -0.20 [-0.28 to -0.12], P < .001; tree: -0.42 [-0.58 to -0.26], P < .001; ragweed: -0.36 [-0.55 to -0.17], P < .001; HDM: -0.28 [-0.39 to -0.17], P < .001). Furthermore, significant improvements versus placebo for all 4 SQ SLIT tablets were seen across the 7 individual domains.
CONCLUSIONS
The proven efficacy of SQ SLIT tablets to reduce symptoms across 4 of the most common respiratory allergens is supported by concurrent significant improvements in RQLQ scores overall and for all 7 domains.
Topics: Humans; Quality of Life; Sublingual Immunotherapy; Adult; Conjunctivitis, Allergic; Allergens; Pyroglyphidae; Rhinitis, Allergic; Animals; Ambrosia; Tablets; Male; Female; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic; Poaceae; Trees; Clinical Trials, Phase II as Topic; Treatment Outcome
PubMed: 38307205
DOI: 10.1016/j.jaip.2024.01.038 -
American Journal of Physiology. Lung... Dec 2023Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. DNA methylation is one form of epigenetic modification that regulates gene...
Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. DNA methylation is one form of epigenetic modification that regulates gene expression and is both inherited and modified by environmental exposures throughout life. Prenatal development is a particularly vulnerable time period during which exposure to maternal asthma increases asthma risk in offspring. How maternal asthma affects DNA methylation in offspring and what the consequences of differential methylation are in subsequent generations are not fully known. In this study, we tested the effects of grandmaternal house dust mite (HDM) allergen sensitization during pregnancy on airway physiology and inflammation in HDM-sensitized and challenged second-generation mice. We also tested the effects of grandmaternal HDM sensitization on tissue-specific DNA methylation in allergen-naïve and -sensitized second-generation mice. Descendants of both allergen- and vehicle-exposed grandmaternal founders exhibited airway hyperreactivity after HDM sensitization. However, grandmaternal allergen sensitization significantly potentiated airway hyperreactivity and altered the epigenomic trajectory in second-generation offspring after HDM sensitization compared with HDM-sensitized offspring from vehicle-exposed founders. As a result, biological processes and signaling pathways associated with epigenetic modifications were distinct between lineages. A targeted analysis of pathway-associated gene expression found that Smad3 was significantly dysregulated as a result of grandmaternal allergen sensitization. These data show that grandmaternal allergen exposure during pregnancy establishes a unique epigenetic trajectory that reprograms allergen responses in second-generation offspring and may contribute to asthma risk. Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. This study shows that maternal allergen exposure during pregnancy promotes unique epigenetic trajectories in second-generation offspring at baseline and in response to allergen sensitization, which is associated with the potentiation of airway hyperreactivity. These effects are one mechanism by which maternal asthma may influence the inheritance of asthma risk.
Topics: Pregnancy; Humans; Female; Mice; Animals; Allergens; Epigenomics; Prenatal Exposure Delayed Effects; Asthma; Disease Susceptibility; Epigenesis, Genetic; Pyroglyphidae
PubMed: 37814791
DOI: 10.1152/ajplung.00103.2023 -
Scientific Reports Oct 2023A subgroup of patients suffering from atopic dermatitis (AD) does not respond to biologics therapy targeting the key players of type-2 inflammation, and it is an ongoing...
A subgroup of patients suffering from atopic dermatitis (AD) does not respond to biologics therapy targeting the key players of type-2 inflammation, and it is an ongoing discussion whether skin-infiltrating Th17 cells may underlie this phenomenon. This study aimed to investigate the potential of allergen-induced, immune-cell derived IL-17 on the induction of inflammatory processes in keratinocytes. Peripheral blood mononuclear cells derived from respectively sensitized AD patients were stimulated with house dust mite (HDM) extract and cell culture supernatants were applied subsequently in absence or presence of secukinumab to primary human keratinocytes. Hereby we confirm that the immune response of sensitized AD patients to HDM contains aside from type-2 cytokines significant amounts of IL-17. Blocking IL-17 efficiently reduced the stimulation-induced changes in keratinocyte gene expression. IL-17-dependent transcriptional changes included increased expression of the cytokines IL-20 and IL-24 as well as Suppressor of Cytokine Siganling 3 (SOCS3), a negative feedback-regulator of the STAT3/IL-17/IL-24 immune response. We conclude that the immune response to HDM can induce pro-inflammatory cytokines from keratinocytes in AD, which in part is mediated via IL-17. Targeting IL-17 may turn out to be a reasonable alternative therapy in a subgroup of patients with moderate to severe AD and HDM sensitization.
Topics: Animals; Humans; Allergens; Cytokines; Dermatitis, Atopic; Dermatophagoides pteronyssinus; Interleukin-17; Keratinocytes; Leukocytes, Mononuclear; Pyroglyphidae
PubMed: 37789035
DOI: 10.1038/s41598-023-42595-z