Role of allergen immunotherapy and biologics in allergic diseases

Current Opinion in Immunology, Journal Year: 2024, Volume and Issue: 91, P. 102494 - 102494

Published: Oct. 1, 2024

Language: Английский

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Identification of mitochondria-related biomarkers in childhood allergic asthma

BMC Medical Genomics, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 23, 2024

Abstract Background The mechanism of mitochondria-related genes (MRGs) in childhood allergic asthma (CAS) was unclear. aim this study to find new biomarkers related MRGs CAS. Methods This research utilized two CAS-related datasets (GSE40888 and GSE40732) extracted 40 from the MitoCarta3.0 Database. Initially, differential expression analysis performed on CAS control samples GSE40888 dataset obtain differentially expressed (DEGs). Differentially (DE-MRGs) were obtained by overlapping DEGs MRGs. Protein protein interactions (PPI) network DE-MRGs created top 10 degree ranking Maximal Clique Centrality (MCC) algorithm defined as feature genes. Hub intersection Least absolute shrinkage selection operator (LASSO) EXtreme Gradient Boosting (XGBoost) algorithms. Additionally, validation conducted, functional enrichment analysis, immune infiltration finished, transcription factors (TFs)-miRNA-mRNA regulatory constructed. Results A total 1505 GSE40888, 44 obtained. PPI based these revealed strong between ADCK5 MFN1, BNIP3 NBR1. Four hub ( NDUFAF7 , MTIF3 MRPS26 NDUFAF1 ) taking LASSO XGBoost algorithms signature which PPI. In addition, genes-based alignment diagram showed good diagnostic performance. results Gene Set Enrichment Analysis (GSEA) suggested that closely mismatch repair. B cells naive significantly groups, most strongly negatively correlated with naive. may have influenced inflammatory response patients affecting functions. quantitative real-time polymerase chain reaction (qRT‒PCR) four all down-regulated samples. Conclusion identified an MRGs-related CAS, provides some reference for further

Language: Английский

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Cord blood methylation at TNFRSF17 is associated with early allergic phenotypes

Immunologic Research, Journal Year: 2024, Volume and Issue: unknown

Published: July 31, 2024

Abstract Food allergy and eczema are the earliest allergic phenotypes in childhood. These diseases could be related to either IgE-mediated or non-IgE-mediated reactions allergen. TNFRSF17 is a key molecule B cell maturation important both types of responses. We conducted study comparing relative expression methylation status at regard child’s early atopic sensitisation phenotypes. In recruited population 200 women 174 children with available clinical data (physical examination by allergist antigen-specific IgE measurements), 78 cord blood samples were included gene analysis (relative GAPDH as reference RT-PCR) 96 microarray DNA (whole genome profile Infinium MethylationEPIC). The altered pattern single cg04453550 mean upstream was observed who developed food and/or change mirrored expression. inhalant allergens not significantly associated TNFRSF17. conclusion, sites birth

Language: Английский

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Allergy discordant twins do not exhibit differences in gene expression in non‐switched and switched B cells

Allergy, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Allergy is a globally spread affliction that based on dysregulation of immune responses towards 'harmless' antigens.1 B cells and their regulation are also involved in mechanisms allergic diseases.2, 3 They produce the IgE essential for allergen-induced mast cell basophil degranulation.4 The common consensus closely tied to tolerance allergy.2, 5 In allergy, this likely dysfunctional, resulting different B-cell behaviours. Therefore, we suspected from individuals may differ class-switching potential or process, making them more prone allergies. We hypothesized there would be significantly expressions pathways related activation, isotype switching correlating symptoms. had 16 twin pairs were either healthy, allergy discordant concordant (Tables S1–S4). donors monozygotic mainly timothy grass, birch tree pollen and/or house dust mites; none taken allergen-immunotherapy. sorted switched unswitched (Figure S1) bio-banked PBMCs, extracted RNA, depleted ribosomal performed 100 bp single-end RNA sequencing Illumina Novaseq 6000 platform.6 Unbiased clustering samples 1A), excluding long non-coding showed main influences descending order versus non-switched cells, then concordance status. degree by status varies, yet no within discordance clusters both suggesting it confounding factor. An individuals' little significant impact overall clustering. same holds true PCA analysis top 300 genes while separated gender 1B). Comparing healthy twins could greatly influenced factors like pair similarities grouping instead actual health compared avoid these gene expression analysis. comparison, neither nor show traditionally associated with allergies (Table S5). A log fold change greater than 0.5 p-value .05 gave FDR 0.9999. Adjusting an below 0.05 (p-value <.00001) resulted differentially expressed five without pathway cells. Using parameters, did not find differences regulations wider scale between allergy-discordant twins. confirmed do group 2A). Pathway does reveal any cohesive (allergy vs. healthy) 2B). One upregulated genes, cycle but directly functions. Our results indication general as underlying cause Any might exist too subtle observed across propose distinctions non-allergic only noticeable allergen-specific These effects probably overshadowed variability among due rarity population. Since study focused tissue-resident exhibit properties. M.A. conceived designed study. K.N. I.C. provided S.S. W.V. planned experiments. P.S., M.Y. helped H.B. bioinformatics graphics. wrote manuscript. K.N., reviewed authors thank all participants Stanford registry donated blood Functional Genomics Center Zürich (FGCZ) work support bioinformatics. This was supported funding Swiss National Science Funds (#31003–201053/320030–159870 M.A.) FreeNovation grant Novartis Research Foundation (to W.V.). declare conflict interest relation work. data findings available corresponding author upon reasonable request. Data S1. Please note: publisher responsible content functionality supporting information supplied authors. queries (other missing content) should directed article.

Language: Английский

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Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 26, 2024

Abstract Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance pollen allergy. However, molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is comprehensive immunological cellular characterization during AIT initiation phase, whereas secondary outcomes are serological and Th2-cell-type-specific transcriptomic analyses. Here we apply multilayer-omics approach reveal dynamic peripheral landscapes AIT-initiation phase in allergy patients (VAP) versus pollen-allergic healthy controls. Already at baseline, VAP exhibit altered abundances several cell types, including classical monocytes (cMono), CD4 + hybrid type 1-type 17 cells (Th1-Th17 or Th1/17) CD8 counterparts (Tc1-Tc17 Tc1/17). At 8-24 h following launch VAP, identify uniform AIT-elicited pulse late-transitional/IL-10-producing B cells, IL-6 signaling within Th2 non-inflammatory serum-IL-6 levels. Sequential induction activation survival protein markers also immediately occur. A disequilibrium between serum cMono baseline restored day seven launch. Our longitudinal analysis discovers initiation-phase insect-venom that secure long-term outcomes. Trial number: NCT02931955.

Language: Английский

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Editorial: Women in primary immunodeficiencies

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 12, 2023

EDITORIAL article Front. Immunol., 12 October 2023Sec. Primary Immunodeficiencies Volume 14 - 2023 | https://doi.org/10.3389/fimmu.2023.1268595

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Deep immune profiling of chronic rhinosinusitis in allergic and non-allergic cohorts using mass cytometry

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 22, 2023

ABSTRACT Background Chronic rhinosinusitis (CRS) is characterized by persistent nasal and paranasal sinus mucosa inflammation. It comprises two phenotypes, namely CRS with polyps (CRSwNP) without (CRSsNP). CRSwNP can be associated asthma hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in a syndrome known as NSAID-exacerbated respiratory disease (N-ERD). Furthermore, frequently intertwines allergies. Objective This study investigated the phenotypic characteristics of peripheral blood mononuclear cells (PBMCs) within cohorts patients, additionally examining influence comorbid allergies on these parameters. Methods 24 participants were grouped into controls, CRSsNP, CRSwNP, N-ERD ( n=6 /group), half patients each group having Levels cytokines quantified secretions sera. The abundance features immune PBMCs evaluated through mass cytometry clustering methods. Results showed heightened type 2 cytokine levels. Mass analysis revealed increased activated naive B cell levels N-ERD, while resting higher CRSsNP. Th2a did not differ between subtypes but significantly elevated allergic subjects. In had lower CXCR5 CD45RA expression, NK displayed reduced CD56 Conclusions There are distinct immunological phenotypes allergy, Capsule summary examines profiles different allergy highlighting intricacies differences allergy.

Language: Английский

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