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Allergology International : Official... Oct 2023We aimed to compare the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) with standardized house dust mite (HDM) extract...
BACKGROUND
We aimed to compare the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) with standardized house dust mite (HDM) extract for allergic rhinitis.
METHODS
Participants with allergic rhinitis selected their treatment between HDM SCIT or HDM SLIT, according to their wishes. We prospectively followed symptoms of allergic rhinitis using the allergic rhinitis symptom medication score (ARSMS), along with adverse reactions, during the dose escalation and maintenance phases for two years. We compared the outcomes between propensity score-matched groups to adjust the confounding factors.
RESULTS
After propensity score matching, 88 patients in the HDM SCIT (n = 44) and HDM SLIT groups (n = 44) remained for analysis. The HDM SCIT group showed significantly earlier effectiveness than the HDM SLIT group (median time to decrease in ARSMS [≥2 points]: 5.5 vs. 18.0 months, p < 0.001). The incidence of systemic reactions was not significantly different between the two groups in the dose escalation phase (68.2% vs. 56.8%, p = 0.379). In the maintenance phase, the incidence of systemic reactions was higher in the HDM SCIT group than in the HDM SLIT group (18.2% vs. 0%, p < 0.006). All 44 patients in the HDM SCIT group completed two years of treatment, while nine patients in the HDM SLIT group discontinued treatment.
CONCLUSIONS
The HDM SCIT group showed an earlier onset of therapeutic effect and a lower discontinuation rate than the HDM SLIT group, although more severe systemic reactions were observed during the maintenance phase.
Topics: Animals; Humans; Child; Sublingual Immunotherapy; Desensitization, Immunologic; Prospective Studies; Pyroglyphidae; Injections, Subcutaneous; Rhinitis, Allergic; Allergens; Treatment Outcome; Antigens, Dermatophagoides
PubMed: 36918306
DOI: 10.1016/j.alit.2023.02.007 -
International Archives of Allergy and... 2024Allergen-specific immunotherapy (AIT), an established treatment for allergic diseases, prevents the development of other allergic manifestations. Although the mechanisms...
BACKGROUND
Allergen-specific immunotherapy (AIT), an established treatment for allergic diseases, prevents the development of other allergic manifestations. Although the mechanisms remain unclear, AIT has been shown to reduce basophil activation (BA) against nontarget allergens.
OBJECTIVES
The aim of this study was to assess immunological changes in Dermatophagoides farinae (Der f) after Japanese cedar pollen (JCP)-based subcutaneous immunotherapy (SCIT) monotherapy.
METHOD
The data of 16 patients (age: 6-37 years) with JCP-induced allergic rhinitis who were sensitive to Der f (serum Der f-specific immunoglobulin E [IgE] level >0.34 kUA/L) and received JCP-based SCIT for 5 years were reviewed retrospectively. BA by Der f and JCP extracts and serum-specific IgE and immunoglobulin G4 (IgG4) levels against these allergens were evaluated before and after completing 5 years of JCP-based SCIT monotherapy.
RESULTS
The areas under the dose-response curves of BA by Der f and JCP extracts were significantly reduced (p = 0.02 and p = 0.002, respectively). JCP-specific IgE levels decreased and JCP-specific IgG4 levels increased significantly (p < 0.001 for both), whereas Der f-specific IgE and IgG4 levels did not change significantly.
CONCLUSIONS
JCP-based SCIT monotherapy reduced Der f-specific BA. These findings suggest that JCP-based SCIT has the potential to modulate immune response toward nontarget allergens.
Topics: Animals; Humans; Child; Adolescent; Young Adult; Adult; Rhinitis, Allergic, Seasonal; Pyroglyphidae; Retrospective Studies; Pollen; Cryptomeria; Basophils; Allergens; Dermatophagoides pteronyssinus; Immunoglobulin E; Desensitization, Immunologic; Immunoglobulin G
PubMed: 37852197
DOI: 10.1159/000533724 -
Biomedicine & Pharmacotherapy =... May 2024CpG oligodeoxynucleotide (CpG-ODN; CpG, in short) has been employed as an adjuvant in allergen specific immunotherapy (AIT) to treat allergic diseases. The underlying...
BACKGROUND
CpG oligodeoxynucleotide (CpG-ODN; CpG, in short) has been employed as an adjuvant in allergen specific immunotherapy (AIT) to treat allergic diseases. The underlying mechanism needs to be further explained. The aim of this study is to examine the mechanism by which CpG and dust mite extracts (DME, a specific antigen) alleviate experimental airway allergy.
METHODS
DME was used as the specific allergen to establish an airway allergy mouse model. The mice were directly exposed to DME and CpG through nasal instillations (the CpG.DME therapy). The response of DCs and allergic responses in the airways were assessed using immunological approaches.
RESULTS
The airway allergy reaction was effectively suppressed by CpG.DME therapy. The administration of CpG or DME alone did not have any significant suppressive effects on the airway allergic response. Direct exposure to CpG.DME induced type 1 DCs (DC1s) and plasmacytoid DCs (pDCs), while CpG alone induced DC1s and DME alone induced DC2s in the airway tissues. Both DC1s and pDCs were required for the induction of type 1 regulatory T cells in the airway tissues by CpG.DME therapy. Depletion of either pDCs or DC1s abolished the induction of Tr1 cells, and abolished the suppressive effects on airway allergic response by the CpG.DME therapy.
CONCLUSIONS
Direct exposure to CpG.DME induces DC1s and pDCs in the airway tissues. DC1s in synergy with pDCs induce type 1 regulatory T cells. The CpG.DME therapy is effective in suppressing allergic responses in mice with airway allergy.
Topics: Animals; Dendritic Cells; Oligodeoxyribonucleotides; Mice; Respiratory Hypersensitivity; Mice, Inbred BALB C; T-Lymphocytes, Regulatory; Female; Adjuvants, Immunologic; Allergens; Antigens, Dermatophagoides; Hypersensitivity; Mice, Inbred C57BL; Disease Models, Animal; Pyroglyphidae
PubMed: 38554528
DOI: 10.1016/j.biopha.2024.116510 -
Scientific Reports Jun 2024Mononuclear phagocytes (MNP), including macrophages and dendritic cells form an essential component of primary responses to environmental hazards and toxic exposures....
Mononuclear phagocytes (MNP), including macrophages and dendritic cells form an essential component of primary responses to environmental hazards and toxic exposures. This is particularly important in disease conditions such as asthma and allergic airway disease, where many different cell types are present. In this study, we differentiated CD34+ haematopoietic stem cells towards different populations of MNP in an effort to understand how different cell subtypes present in inflammatory disease microenvironments respond to the common allergen house dust mite (HDM). Using single cell mRNA sequencing, we demonstrate that macrophage subtypes MC and MLC display different patterns of gene expression after HDM challenge, noted especially for the chemokines CXCL5, CXCL8, CCL5 and CCL15. MLC alternatively activated macrophages displayed the greatest changes in expression, while neutrophil and monocyte populations did not respond. Further work investigated how pollutant diesel exhaust particles could modify these transcriptional responses and revealed that CXC but not CC type chemokines were further upregulated. Through the use of diesel particles with adsorbed material removed, we suggest that soluble pollutants on these particles are the active constituents responsible for the modifying effects on HDM. This study highlights that environmental exposures may influence tissue responses dependent on which MNP cell type is present, and that these should be considerations when modelling such events in vitro. Understanding the nuanced responsiveness of different immune cell types to allergen and pollutant exposure also contributes to a better understanding of how these exposures influence the development and exacerbation of human disease.
Topics: Animals; Pyroglyphidae; Humans; Phagocytes; Macrophages; Allergens; Vehicle Emissions; Hematopoietic Stem Cells; Dendritic Cells; Gene Expression Regulation
PubMed: 38902328
DOI: 10.1038/s41598-024-64783-1 -
Allergology International : Official... Jul 2024This study aimed to clarify the diagnostic and predictive factors for perennial allergic rhinitis (PAR) onset in children by analyzing the results of the Chiba High-risk...
BACKGROUND
This study aimed to clarify the diagnostic and predictive factors for perennial allergic rhinitis (PAR) onset in children by analyzing the results of the Chiba High-risk Birth Cohort for Allergy study, which examined newborns with a family history of allergies.
METHODS
Overall, 306 pregnant women were recruited. Their newborns were examined by otolaryngologists and pediatric allergists at 1, 2, and 5 years of age. Participants with clinical and laboratory data available at all consultation points were considered eligible.
RESULTS
Among 187 eligible participants, the prevalence rates of PAR were 2.1%, 4.3%, and 24.1% at 1, 2, and 5 years of age, respectively. AR-specific nasal local findings and eosinophils in nasal smear were observed in a substantial number of patients with PAR at 1 and 2 years of age. Factors present up to 2 years of age that were associated with PAR onset at 5 years of age, in descending order, were as follows: sensitization to house dust mites (HDM), nasal eosinophilia, and sensitization to cat dander. In 44 cases with HDM sensitization, nasal eosinophilia up to 2 years of age achieved a sensitivity of 76.0% and a specificity of 73.7% for predicting PAR onset at 5 years.
CONCLUSIONS
Rhinitis findings and nasal eosinophilia are useful auxiliary diagnostic items for pediatric PAR. Sensitization to HDM and nasal eosinophilia were the most influential factors associated with future PAR onset. A combination of these factors may facilitate the prediction of PAR onset.
Topics: Humans; Female; Child, Preschool; Male; Infant; Rhinitis, Allergic, Perennial; Allergens; Prevalence; Infant, Newborn; Risk Factors; Japan; Animals; Pyroglyphidae; Eosinophilia; Pregnancy
PubMed: 38350815
DOI: 10.1016/j.alit.2024.01.012 -
Biomedicine & Pharmacotherapy =... Jul 2024Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica, known as...
Reynoutria japonica consisted of emodin-8-β-D-glucoside ameliorates Dermatophagoides farinae extract-induced atopic dermatitis-like skin inflammation in mice by inhibiting JAK/STAT signaling.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica, known as Huzhang in traditional Chinese Medicine, can enhance blood circulation to eliminate wind pathogens and terminate coughing. Despite pharmacological evidence supporting the efficacy of R. japonica in suppressing edema-induced skin inflammation or connective tissue diseases, its pharmaceutical potential for treating AD-like skin inflammation remains unexplored. This study investigated the possible effects of R. japonica ethanol extract (RJE) on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation in NC/Nga mice. To elucidate the underlying mechanisms by which RJE inhibits skin inflammation, we examined the effect of RJE on IFN-γ/TNF-α-induced signal transducer and activator of transcription (STAT) signaling in human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Our findings revealed that RJE mitigates DfE-induced AD-like symptoms and skin barrier disruptions in mouse skin lesions. Moreover, RJE attenuated DfE-induced mast cell infiltration and serum levels of inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-23, IFN-γ, TNF-α, and GM-CSF). RJE also inhibited IFN-γ/TNF-α-induced chemokine levels and STAT3 phosphorylation in HEKs and HDFs. Virtual binding analysis of the RJE components suggested that emodin-8-β-D-glucoside binds to Janus kinase (JAK) 1/2, thereby suppressing STAT signaling, which was confirmed by Western blot analysis. In conclusion, our results suggest that RJE may alleviate DfE-induced skin barrier dysfunction by inhibiting JAK/STAT signaling and the proinflammatory immune response through the suppression of inflammatory mediators in AD-like skin disease. These findings suggest that RJE has potential as an effective therapy for AD management.
Topics: Animals; Dermatitis, Atopic; Signal Transduction; Mice; Dermatophagoides farinae; STAT Transcription Factors; Janus Kinases; Humans; Glucosides; Cytokines; Male; Skin; Emodin; Keratinocytes; Plant Extracts; Inflammation
PubMed: 38788600
DOI: 10.1016/j.biopha.2024.116765 -
Chinese Medical Journal Sep 2023
Topics: Animals; Humans; Thymic Stromal Lymphopoietin; Pyroglyphidae; Cytokines; Asthma; Respiratory System; Epithelial Cells
PubMed: 37469013
DOI: 10.1097/CM9.0000000000002615 -
PeerJ 2024Allergen extracts and recombinant allergens are used in allergy diagnostics and immunotherapy. Since allergen extracts from different manufacturers lack proper...
BACKGROUND
Allergen extracts and recombinant allergens are used in allergy diagnostics and immunotherapy. Since allergen extracts from different manufacturers lack proper standardization regarding their composition, monoclonal antibodies (MAbs) against specific allergen components can be used for their identification and quantification in allergen extracts. This study aimed to generate MAbs against allergen Der p 21 of for the analysis of allergen extracts.
METHODS
Recombinant Der p 21 was expressed in and purified using affinity chromatography. MAbs against Der p 21 were generated using hybridoma technology. House dust mite (HDM) allergen extracts were analyzed using the newly developed sandwich enzyme-linked immunosorbent assay, Western blotting and microarray immunoassay.
RESULTS
MAbs raised against recombinant Der p 21 were characterized in detail and proven to be reactive with natural Der p 21. Highly specific sandwich enzyme-linked immunosorbent assay for the quantification of Der p 21 was developed and optimized. The allergen was detected and its concentration was determined in only three of six analyzed HDM allergen extracts from different manufacturers.
CONCLUSION
HDM analysis by MAb-based immunoassays shows their differences in allergen composition. The results demonstrate the importance of allergen-specific MAbs as a tool for the characterization of allergen extracts and the need for their appropriate standardization before their use for allergy diagnostics or immunotherapy.
Topics: Antibodies, Monoclonal; Animals; Antigens, Dermatophagoides; Enzyme-Linked Immunosorbent Assay; Recombinant Proteins; Arthropod Proteins; Mice; Allergens; Blotting, Western; Pyroglyphidae; Mice, Inbred BALB C
PubMed: 38646484
DOI: 10.7717/peerj.17233 -
International Journal of Molecular... Feb 2024Long-term oral ingestion of unheated yuzu seed oil in humans reduces lipid peroxides in the blood. Moreover, yuzu seed oil contains limonin, which can induce antioxidant...
Long-term oral ingestion of unheated yuzu seed oil in humans reduces lipid peroxides in the blood. Moreover, yuzu seed oil contains limonin, which can induce antioxidant and anti-inflammatory effects by activating the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Previously, Nrf2 has been shown to reduce atopic dermatitis (AD). Therefore, we hypothesized that ingesting unheated yuzu seed oil can regulate AD through Nrf2. An AD model was established using NC/Nga mice through repeated local exposure to mite antigens. Unheated and purified yuzu seed oil (100 µL/mice) or water (control, 100 µL/mice) was administered orally once a day using a gastric cannula for rodents for 28 days. On day 28, mice in the unheated yuzu seed oil group exhibited significantly lower clinical skin severity scores and ear thickness than those in the purified yuzu seed oil and water groups. Serum histamine levels remained unaltered among the three AD-induced groups. Serum body (Dfb)-specific immunoglobulin E (IgE) levels were significantly lower in the unheated yuzu seed oil group. Oral ingestion of yuzu seed oil in NC/Nga AD model mice significantly suppressed dermatitis deterioration and decreased serum IgE levels. Clinical trials ( = 41) have already confirmed that unheated yuzu oil is safe for long-term intake, further suggesting its potential use in improving AD symptoms.
Topics: Humans; Mice; Animals; Dermatitis, Atopic; NF-E2-Related Factor 2; Skin; Immunoglobulin E; Dermatophagoides farinae; Eating; Plant Oils; Disease Models, Animal
PubMed: 38473936
DOI: 10.3390/ijms25052689 -
Allergology International : Official... Jul 2024Although it has been reported that cellular senescence is important in the pathogenesis of asthma, the differential effects of diesel exhaust particle (DEP)-induced...
BACKGROUND
Although it has been reported that cellular senescence is important in the pathogenesis of asthma, the differential effects of diesel exhaust particle (DEP)-induced cellular senescence on the development of asthma according to age have not been thoroughly studied.
METHODS
We first confirmed that DEP induced cellular senescence in mouse lungs, and then that DEP-induced cellular senescence followed by intranasal instillation of a low-dose house dust mite (HDM) allergen resulted in murine asthma. Second, we examined age-dependent differential effects using 6-week-old (young) and 18-month-old mice (old), and tested whether the mammalian target of the rapamycin (mTOR) pathway plays an important role in this process. Finally, we performed in vitro experiments using human bronchial epithelial cells (HBEC) originating from young and elderly adults to identify the underlying mechanisms.
RESULTS
DEP induced cellular senescence in the airway epithelial cells of young and old mice characterized by increased senescence-associated beta-galactosidase, S100A8/9, and high mobility group box 1 (HMGB1) expressions. DEP-induced cellular senescence with subsequent exposure to a low-dose HDM allergen resulted in asthma in young and old mice. Rapamycin (mTOR pathway inhibitor) administration before DEP instillation significantly attenuated these asthmatic features. In addition, after treatment with a low-dose HDM allergen, S100A9 and HMGB1 over-expressed HBEC originating from young and elderly adults greatly activated co-cultured monocyte-derived dendritic cells (DCs).
CONCLUSIONS
This study showed that DEP-induced senescence made both young and old mice susceptible to allergic sensitization and resultant asthma development by enhancing DC activation. Public health efforts to reduce DEP exposure are warranted.
Topics: Animals; Asthma; Cellular Senescence; Vehicle Emissions; Mice; TOR Serine-Threonine Kinases; Humans; Disease Models, Animal; Epithelial Cells; Female; Allergens; Age Factors; Pyroglyphidae; Signal Transduction
PubMed: 38350817
DOI: 10.1016/j.alit.2024.01.010