Local IgE Production Research Articles

Fecal IgE Analyses Reveal a Role for Stratifying Peanut-Allergic Patients.

Peanut allergy (PA) is an IgE-mediated food allergy with variable clinical outcomes. Mild-to-severe symptoms affect various organs and, often, the gastrointestinal tract. The role of intestine-derived IgE antibodies in astrointestinal PA symptoms is poorly understood. This study aimed to examine fecal IgE responses in PA as a novel approach to patient endotyping. Feces and serum samples were collected from peanut-allergic and healthy children (n=26) to identify IgE and cytokines using multiplex assays. Shotgun metagenomics DNA sequencing and allergen database comparisons made it possible to identify microbial peptides with homology to known allergens. Compared to controls, fecal IgE signatures showed broad diversity and increased levels for 13 allergens, including food, venom, contact, and respiratory allergens (P<.01-.0001). Overall, fecal IgE patterns were negatively correlated compared to sera IgE patterns in PA patients, with the greatest differences recorded for peanut allergens (P<.0001). For 83% of the allergens recognized by fecal IgE, we found bacterial homologs from PA patients' gut microbiome (eg, thaumatin-like protein Acinetobacter baumannii vs Act d 2, 109/124 aa identical). Compared to controls, PA patients had higher levels of fecal IgA, IL-22, and auto-IgE binding to their own fecal proteins (P<.001). Finally, levels of fecal IgE correlated with abdominal pain scores (P<.0001), suggesting a link between local IgE production and clinical outcomes. Fecal IgE release from the intestinal mucosa could be an underlying mechanism of severe abdominal pain through the association between leaky gut epithelia and anticommensal TH2 responses in PA.

Characteristics of upper respiratory tract rhinovirus in children with allergic rhinitis and its role in disease severity.

Our study revealed high human rhinovirus (HRV) detection rate in children with allergic rhinitis (AR), and HRV infection (A, B, or C species) is positively associated with the symptom severity in AR children. Elevated nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 levels suggest a potential pathogenic mechanism by which HRV infection induces nasal type 2 immune/inflammation responses and local IgE production in AR patients. In addition, etiological analysis found that the main prevalent HRV species in AR children are A and B (~80%), which is different from acute respiratory infection and asthma exacerbation, where species A and C are dominant. The data reveal the distinct species prevalence characteristics of HRV infection in AR. Finally, we isolated all three species of HRV strains from nasal cavity of AR children with varying degrees of antigenic epitope mutations and in vitro infectivity, highlighting the importance of strengthening monitoring and intervention for respiratory HRV infection in AR children.

Staphylococcus aureus Biofilm-Secreted Factors Cause Mucosal Damage, Mast Cell Infiltration, and Goblet Cell Hyperplasia in a Rat Rhinosinusitis Model.

Chronic rhinosinusitis (CRS) is an inflammatory condition of the sinonasal mucosa. Despite being a common health issue, the exact cause of CRS is yet to be understood. However, research suggests that Staphylococcus aureus, particularly in its biofilm form, is associated with the disease. This study aimed to investigate the impact of long-term exposure to secreted factors of Staphylococcus aureus biofilm (SABSFs), harvested from clinical isolates of non-CRS carrier and CRS patients, on the nasal mucosa in a rat model. Animals were randomised (n = 5/group) to receive daily intranasal instillations of 40 μL (200 μg/μL) SABSFs for 28 days or vehicle control. The sinonasal samples were analysed through histopathology and transcriptome profiling. The results showed that all three intervention groups displayed significant lymphocytic infiltration (p ≤ 0.05). However, only the SABSFs collected from the CRSwNP patient caused significant mucosal damage, mast cell infiltration, and goblet cell hyperplasia compared to the control. The transcriptomics results indicated that SABSFs significantly enriched multiple inflammatory pathways and showed distinct transcriptional expression differences between the control group and the SABSFs collected from CRS patients (p ≤ 0.05). Additionally, the SABSF challenges induced the expression of IgA and IgG but not IgE. This in vivo study indicates that long-term exposure to SABSFs leads to an inflammatory response in the nasal mucosa with increased severity for S. aureus isolated from a CRSwNP patient. Moreover, exposure to SABSFs does not induce local production of IgE.

Validation and shortcomings of the most common mouse model of chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis (CRS) is a highly prevalent airway disease worldwide. Whereas eosinophilic CRS with nasal polyps (eCRSwNP) represents its most severe phenotype, pathogenic mechanisms remain poorly understood despite a wide spectrum of in vitro and in vivo experimental models. A mouse model of experimental ovalbumin (OVA)-induced airway allergy with coadministration of Staphylococcus aureus enterotoxin B (SEB) has been widely used to study eosinophilic eCRSwNP. This study revisits the features of this model and its suitability for studying eCRS. We implemented the most used eCRSwNP mouse model based on OVA+SEB intranasal challenges. Readouts including inflammatory features by (immuno)histology of the sinonasal epithelium (NP formation, eosinophils, epithelial and basement membrane thickness, fibrosis, goblet cells, Charcot-Leyden crystals (CLC)-like, tight junctions) and IgE production by enzyme-linked immunosorbent assay (ELISA), were compared to features of the corresponding human disease. The OVA+SEB model induced eosinophilic inflammation of upper and lower airways, with epithelial and basement membrane thickening, goblet cell hyperplasia and subepithelial fibrosis in the sinuses, along increased IgE production. Except local IgE in nasal lavage (NL), which was only increased in OVA+SEB group, all other features did not differ between OVA and OVA+SEB groups. Macro- or microscopic NP were not detected. With the notable exception of local IgE production, the addition of SEB did not induce additional inflammatory or structural change in the sinuses from mice exposed to and challenged with OVA. This model might represent a model for severe upper airway allergy rather than a specific model of human eCRSwNP.

MZB1-expressing cells are essential for local immunoglobulin production in chronic rhinosinusitis with nasal polyps

BackgroundThe expression of MZB1 genes is significantly elevated in patients who have chronic rhinosinusitis with nasal polyp (CRSwNP) disease compared with healthy controls. ObjectiveTo characterize MZB1-positive B cells in CRSwNP and to estimate the contribution of distinct subsets of B cells to the local overproduction of immunoglobulins. MethodsSingle-cell RNA-sequencing with Cellular Indexing of Transcriptomes and Epitopes by Sequencing technology, Switching Mechanism At the 5′ end of RNA Template sequencing, flow cytometry, immunohistochemistry and immunofluorescence staining, Western blot, QuantiGene Plex assay, B-cell ImmunoSpot assay, Luminex assay, and enzyme-linked immunosorbent assay were performed. ResultsSignificantly higher mRNA expression of MZB1 and HSP90B1 was found in type 2 CRSwNP compared with controls. In CRSwNP, MZB1 expression correlated with the local production of IgE. MZB1 could be colocalized with plasma and mature B cells, especially marginal zone (MZ) B cells. Single-cell transcriptome and epitope studies revealed prominent populations of B cells in type 2 CRSwNP with unexpectedly high MZB1 gene expression. The MZ B-cell population was significantly increased in CRSwNP compared with healthy controls in both peripheral blood mononuclear cells and nasal tissue single-cell suspensions. When those single cells were cultured overnight, the MZ B-cell numbers were positively correlated with local IgE production but negatively correlated with local IgM production. In vitro, MZB1 stimulation up-regulated the mRNA expression of IgE. ConclusionMZB1 was primarily expressed by plasma and mature B cells in nasal mucosa. MZB1 expression level was increased in CRSwNP compared with controls. MZB1 contributed to the local IgE production in type 2 CRSwNP.

Asthmatics only sensitized to Staphylococcus aureus enterotoxins have more exacerbations, airflow limitation, and higher levels of sputum IL-5 and IgE.

Staphylococcus aureus Enterotoxins (SE) may act as superantigens and induce an intense T cell activation causing local production of polyclonal IgE and resultant eosinophil activation. To assess whether asthma with sensitization to SE but not to common aero-allergens (AA) displays different inflammatory characteristics. We conducted a prospective study on a series of 110 consecutive patients with asthma recruited from the University Asthma Clinic of Liege. We compared clinical, functional and inflammatory characteristics of this general population of asthmatics categorized in 4 groups according to sensitization to AA and/or SE. We also compared sputum supernatant cytokines in patients sensitized to SE or not. Asthmatics only sensitized to AA represented 30%, while 29% were sensitized to both AA and SE. One fifth of the population had no specific IgE. Sensitization to SE but not to AA (21%) was associated with later onset of disease, higher rate of exacerbations, nasal polyps and more severe airway obstruction. As for airway type-2 biomarkers, patients presenting with specific IgE against SE (SE-IgE) displayed higher FeNO, sputum IgE and sputum IL-5 levels but not IL-4. We confirm that the presence of SE-IgE is associated with elevated serum IgE to levels well above those observed in patients only sensitized to AA. Our study suggests that asthma specialists should measure SE-IgE during the phenotyping process as it may allow the identification of a subgroup of patients with more asthma exacerbations, more nasal polyposis and chronic sinusitis, lower lung function and more intense type-2 inflammation.

Local Allergen-Specific IgE Production in Turbinate Tissue of Pediatric Patients.

The objective of this study is to compare serum allergen-specific IgE to IgE levels in nasal tissue taken from the inferior turbinates of pediatric patients undergoing turbinate reduction. Twenty-six pediatric patients were recruited at the time of turbinate reduction surgery. At the time of recruitment, parents of patients completed the validated 22 item Sinonasal Outcome Test (SNOT-22) to describe symptoms prior to surgery. A sample of turbinate tissue was taken during turbinate reduction and blood was collected. Tissue and serum IgE were measured and differences in the group characteristics were evaluated using Chi-square tests for binary variables and Wilcoxon-Mann-Whitney tests for continuous variables. Student's t test was used to assess differences in means of total SNOT-22 scoring between the groups, and Wilcoxon-Mann-Whitney tests were used again for the rest of the SNOT-22 analysis. Levels of IgE in the serum were compared to levels in the turbinate tissue from all patients for each individual allergen. Every allergen except Alternaria displayed significant correlation between the serum and turbinate IgE levels. Additionally, each allergen except Alternaria and oak tree resulted in a strong correlation (r > .7) based on the correlation coefficients. Levels of Alternaria were found to be poorly correlative between serum and turbinate tissue, and significance was not achieved (r = -.346, P = .11). Certain allergen-specific IgE antibodies in the nasal mucosa seem to be highly associated with those in the serum, based upon the significant correlations we found between the two.

Lung memory B cells promote local IgE production in the respiratory tract

Abstract Allergen-specific IgE mediates allergic asthma. IgE responses including class-switch recombination (CSR) to IgE are tightly regulated. However, the regulation of local CSR to IgE at mucosal sites is poorly understood. This study aims to elucidate cellular sources that promote IgE CSR and mechanisms that regulate IgE production in the respiratory tract. To model allergic airway inflammation, we repeatedly administered intranasal ragweed pollen and OVA to mice. We profiled B cell responses to OVA in the lung, the lung-draining mediastinal lymph nodes (medLN), spleen and bone marrow. We used fluorescent reporter mice to track IgE CSR and identify B cell subsets that promote IgE CSR by flow cytometry and microscopy. We found that intranasal allergen exposure elicited robust local B cell responses with the formation of OVA-specific B cells in the medLN and OVA-specific IgE in the airway. OVA-specific germinal center B cells and memory B cells (MBCs) accumulated in the lungs. Using fluorescent reporter mice, we showed that IgG1+ MBCs are the predominant IgE-switching cells. Importantly, the number of IgE-switching MBCs are the highest in the lungs, and IgG1+ MBCs exhibit an increased frequency of IgE CSR in the lungs compared to lymphoid tissues. These suggest that the lung environment favors IgE production. RNA-seq analyses comparing lung and circulating MBCs revealed elevated expression of Tnfsf4 (OX40L) and Icosl on lung MBCs, suggesting a higher propensity for lung MBCs to engage T cells. Together, these data demonstrate that the allergic lung is a major site of IgE CSR with IgG1+ MBCs promoting local IgE CSR. Our ongoing work focuses on delineating the B cell-intrinsic and extrinsic factors that promote IgE production in the respiratory mucosa. Supported by grants from NIH (1F31 HL156459, 5T32 AI007508, 1R21 AI159456)

The histological and microbiological characteristics of bacterial microcolonies in paediatric tonsillar hyperplasia

IntroductionPaediatric tonsillar hyperplasia (TH) is associated with a spectrum of presentations ranging from recurrent tonsillitis (RT) to sleep-disordered breathing (SDB). The underlying pathogenesis of tonsillar hyperplasia remains poorly understood. Previous studies have implicated bacterial microcolonies as targets of host inflammatory cells and as a potential driver of the chronic inflammation seen in TH. The role of atopy in tonsillar hyperplasia is also largely unknown. In this study, we aimed to determine the allergic responses and microbial factors that may influence TH in children. Materials and methodsPaired tonsils and a serum sample were collected from 21 children undergoing tonsillectomy for RT or SDB in the Auckland region. The disposition of immunoglobulin isotypes (IgG, A, M and E) and local inflammatory cells on histological sections of tonsil tissue were determined using immunohistochemistry techniques. Aeroallergen specific IgE (sIgE) and Staphylococcal enterotoxin C specific IgE (SEC-specific IgE) were measured in serum and tonsil tissue using the ImmunoCAP® system. Finally, tonsil bacterial microcolonies were then excised from histological slides using laser microdissection techniques, before undergoing bacterial and fungal amplicon sequencing. ResultsThere were no significant differences in any of the measured variables between children with RT and SDB symptoms. IgE staining was not associated with increased levels of mast cells, leukocytes or plasma cells. However, sIgE positivity was more frequently found in local tissue than in serum (p = 0.025). A significant association was observed between tissue sIgE levels and tissue SEC-specific IgE levels (r2 = 0.95, p = 0.0001). The most abundant bacterial and fungal genera identified in the microcolonies were Fusobacterium, Sphingomonas, Porphyromonas, Prevotella and Malassezia. DiscussionThese results suggest that there is a local IgE response in children with TH. Local IgE production is unrelated to systemic atopy and may play a key role in the pathogenesis of TH. This is the first study to determine the microbial composition of microcolonies in tonsil tissue. These findings enhance current understanding of the microbiology of tonsils in children with TH and have important implications for antibiotic strategies.

Endoplasmic reticulum stress promotes local immunoglobulin E production in allergic rhinitis.

BackgroundThe role of endoplasmic reticulum (ER) stress in the pathogenesis of allergic rhinitis (AR) remains elusive.MethodsReal‐time polymerase chain reaction (RT‐PCR), immunohistochemistry, and western blotting analyses were performed to detect the expression of ER stress and unfolded protein response markers: 78‐kDa glucose‐regulated protein (GRP78), C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6α), spliced X‐box binding protein 1 (sXBP‐1), and phosphorylated eukaryotic initiation factor 2α (p‐eIF2α), in inferior turbinate tissue samples from patients with AR and non‐AR controls. Nasal tissues from patients with AR were cultured ex vivo and treated with 4‐phenylbutyric acid (4‐PBA), an ER stress inhibitor.ResultsCompared to those in non‐AR controls, the mRNA and protein levels of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α were significantly increased in nasal tissues from patients with AR. GRP78 and CHOP were mainly expressed in CD138+ plasma cells in nasal tissues from patients with AR. The frequency of IgE+CD138+ plasma cells was significantly higher in nasal tissues from patients with AR than that in non‐AR controls. IgE levels in nasal secretions and tissues were positively correlated with GRP78 and CHOP mRNA levels in the nasal tissues. After 4‐PBA treatment, the protein expression of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α was significantly reduced in cultured AR‐derived nasal tissues, and IgE levels were simultaneously decreased in cultured supernatants.ConclusionsER stress may be involved in the regulation of local IgE production in patients with AR. Inhibition of ER stress potentially provides a therapeutic avenue in AR by reducing local IgE production.Level of EvidenceNA

Eosinophilic Esophagitis and Microbiota: State of the Art.

Eosinophilic esophagitis (EoE) is a chronic, food-triggered, immune-mediated disease of the oesophagus, clinically characterized by symptoms referred to oesophagal dysfunction, and histologically defined by an eosinophil productive inflammation of the oesophagal mucosa, among other cell types. The involvement of an adaptive Th2-type response to food antigens in EoE was known since 2000; several cytokines and chemokines promote food-specific responses, during which local production of IgE, but also IgG4 derived from plasma cells in lamina propria of oesophagal mucosa might play an important role. Evidence pointing towards a possible role for the innate immunity in EoE has arisen recently. Together, this evidence gives rise to a potential role that the innate immune system in general, and also the microbial pattern recognition receptors (PRRs) might play in EoE pathogenesis. Among PRRs, Toll-like receptors (TLRs) are type-I transmembrane receptors expressed both on epithelial and lamina propria cells with the capacity to distinguish between pathogen and commensal microbes. As TLRs in the different intestinal epithelia represent the primary mechanism of epithelial recognition of bacteria, this evidence underlines that oesophagal TLR-dependent signaling pathways in EoE support the potential implication of microbiota and the innate immune system in the pathogenesis of this disease. The oesophagal mucosa hosts a resident microbiota, although in a smaller population as compared with other districts of the gastrointestinal tract. Few studies have focused on the composition of the microbiota of the normal oesophagus alone. Still, additional information has come from studies investigating the oesophagal microbiota in disease and including healthy patients as controls. Our review aims to describe all the evidence on the oesophagal and intestinal microbiota in patients with EoE to identify the specific features of dysbiosis in this condition.

Prior Exposure to Ortho-Phthalaldehyde Augments IgE-Mediated Immune Responses to Didecyldimethylammonium Chloride: Potential for 2 Commonly Used Antimicrobials to Synergistically Enhance Allergic Disease.

Health-care workers have an increased incidence of allergic disease compared with the general public and are exposed to a variety of high-level disinfectants. Although exposure to these agents has been associated with allergic disease, findings between epidemiology and animal studies often conflict respecting immunological mechanisms. Therefore, we hypothesized that previous exposure to a representative IgE-mediated sensitizer (ortho-phthalaldehyde [OPA]) alters immune responses to a representative T-cell-mediated sensitizer (didecyldimethlyammonium chloride [DDAC]). Here, BALB/c mice were topically exposed to OPA (0.5%) for 3 days, rested, then topically exposed to DDAC (0.0625%, 0.125%, and 0.25%) for 14 days. Coexposure resulted in phenotypic changes in draining lymph node (dLN) cells, including a decreased frequency of CD8+ T cells and increased frequency and number of B cells compared with DDAC-only treated mice. The coexposed mice also had enhanced Th2 responses, including significant alterations in: dLN Il4 (increased), B-cell activation (increased), CD8+ T-cell activation (decreased), and local and systemic IgE production (increased). These changes were not observed if mice were exposed to DDAC prior to OPA. Exposure to OPA alone shows Th2 skewing, indicated by increased activation of skin type 2 innate lymphoid cells, increased frequency and activation of draining lymph node B cells, and increased levels of type 2 cytokines. These findings suggest that the OPA-induced immune environment may alter the response to DDAC, resulting in increased IgE-mediated immune responses. This data may partially explain the discordance between epidemiological and laboratory studies regarding disinfectants and provide insight into the potential immunological implications of mixed chemical exposures.

The roles of B cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) in allergic asthma

Allergic asthma, which is the most common type of asthma, is mediated by the IgE response, and B cells are key drivers of allergic inflammation in the lungs. B cell activation factor (BAFF) and proliferation inducing ligand (APRIL) are members of the TNF superfamily. BAFF and APRIL interact with three receptors, namely the B cell activation factor receptor (BAFF-r), B cell maturation antigen (BCMA), and transmembrane activator; calcium modulator; and cyclophilin ligand interactor (TACI). The interaction of BAFF and APRIL with their receptors induces B cell activation, differentiation, and antibody production. BAFF and APRIL are produced by airway epithelial cells during the response to allergens or infectious agents, and have shown to induce local IgE production, thus establishing allergic inflammation in the airways. BAFF can maintain in inflamed airways during infection and can inhibit regulatory T cells (Tregs), thereby promoting allergic inflammation in the airways. This review aims to outline current knowledge about BAFF/APRIL systems in humans as well as in murine models of allergic asthma. The precise role of BAFF and APRIL and their receptors in allergic asthma remains unclear. Therefore, further studies are required to identify and elucidate their roles in enhancing IgE production and activating immune cells that drive the Th2 effector response and initiate allergic inflammation in asthma. Targeting BAFF/APRIL or their cognate receptors may offer a novel therapeutic approach in asthma treatment.

Nasal IgE in subjects with allergic and non-allergic rhinitis

PurposeThe prevalence of "ocal allergic rhinitis" within individuals suffering from perennial rhinitis remains uncertain, and patients usually are diagnosed with non-allergic rhinitis. The aim of this study was to evaluate the prevalence of a potential "local allergic rhinitis" in subjects suffering from non-allergic rhinitis in a non-selected group of young students. Methods131 students (age 25.0 ± 5.1 years) with a possible allergic rhinitis and 25 non-allergic controls without rhinitis symptoms (age 22.0 ± 2.0 years) were recruited by public postings. 97 of 131 students with rhinitis were tested positive (≥3 mm) to prick testing with 17 frequent allergens at visit 1. Twenty-four 24 subjects with a house dust mite allergy, 21 subjects with a non-allergic rhinitis, and 18 non-allergic controls were further investigated at visit 2. Blood samples were taken, and nasal secretion was examined. In addition, all groups performed a nasal provocation test with house dust mite (HDM). ResultsIn serum and nasal secretion, total IgE and house dust mite specific IgE significantly differed between HDM positive subjects and controls. However, no differences between non-allergic subjects and control subjects were quantifiable. Neither a nasal provocation test nor a nasal IgE to HDM allergens showed a measurable positive response in any of the non-allergic rhinitis subjects as well as the healthy controls, whilst being positive in 13 subjects with HDM allergy. ConclusionsNasal IgE is present in subjects with HDM allergy, but not in non-allergic rhinitis. In the investigated non-selected population, exclusive local production of IgE is absent. By implication, therefore, our findings challenge the emerging concept of local allergic rhinitis.Study identifier at ClinicalTrials.gov: NCT 02810535.

The current state of the knowledge about local allergic rhinitis.

In recent years, a new phenotype of rhinitis has been described; it is characterized by the local production of specific IgE. There isn't any evidence of systemic atopy and it has been called local allergic rhinitis. Understanding the involved physiopathological mechanisms and the behavior of this phenotype translates into the development of strategies and treatments that improve the quality of life of patients with this disease. Below, we present an updated review of the available information regarding this disease and also of the aspects that are yet unresolved.

O-Coumaric acid attenuates atopic dermatitis-like skin inflammation

Abstract Background Hydroxycinnamic acids (coumaric acid; CA) and their derivatives display anti-oxidant and anti-inflammatory effects. CA has three isomers including o-CA, m-CA, and p-CA. Among them, recent report showed the effectiveness of p-CA on skin inflammation. Objective In this study, we investigated the role of o-CA on atopic dermatitis (AD) comparing with p-CA. Methods For the induction of atopic dermatitis (AD)-like skin inflammation, 1,4-dinitrochlorobenzene (DNCB) and house dust mite extract (Dermatophagoides farinae extract, DFE) were applicated repeatedly, and o-CA were orally administered. For mechanism study, tumor necrosis factor (TNF)-α and interferon (IFN)-γ stimulated human keratinocyte cell line (HaCaT) was used. Results In AD-like skin inflammation, the clinical symptoms including the redness, dermal/epidermal thickness, and infiltration of mast cells were significantly reduced by the oral treatment of o-CA. Local inflammatory cytokines expression and systemic production of IgE and IgG2a were also suppressed by the o-CA. In addition, o-CA inhibited the expression of interleukin (IL)-1β, IL-6 and CC-chemokine ligand 17 in TNF-α/IFN-γ stimulated HaCaT cells by the reduction of nuclear translocation of nuclear factor-κB. In all cases, o-CA showed more effectiveness than p-CA. Conclusions These results showed that o-CA could be a potential candidate for AD treatment.

The dialogue between mast cells and B cells worsens the pathology of abdominal aortic aneurysms

The pathology of abdominal aortic aneurysm (AAA) is a life-threatening disease, with no treatment able to stop or slow the growth and rupture of AAAs; the only medical option is surgery. A better understanding of the mechanisms triggering this pathology is therefore needed to design new treatments. Immune effectors play a role in the pathology. In particular, it has been shown that IgE antibodies, mast cells (MCs) and germinal center (GC) B cells, which are known to form an axis of the immune system, accumulate in the adventitia of AAA. Our goal is to test if the MC-B cell-IgE axis triggers a local amplification loop that precipitates the rupture of AAAs. To assess the effect of MCs on AAA healing in vivo, we created a mouse model that develop aneurysm and can be depleted in MCs. In parallel, we characterized the MC–B cell–IgE axis in blood and arterial samples collected from AAA and control patients. We tested, in vitro, the ability of adventitial soluble molecules, especially IgEs, to activate human MCs. We observed that mice which are depleted in MCs during the healing phase of AAA develop smaller aneurysms with elevated collagen density. In human AAA adventitia, MCs are activated, covered by IgEs, and located in the vicinity of GCs, which suggest that they can interact with GC B cells in AAAS. The GC B cells from the adventitia are absent from paired patient blood and some adventitial GC stained positive for IgE. Therefore, adventitial GC probably arise from a local differentiation of B cells and support a local production of IgE. AAA adventitial soluble factors trigger the degranulation of MC and their IgE-dependent production of IL-4, a cytokine required for B cells to produce IgEs ( Fig. 1 ). Our data suggest that locally produced IgE directed against lesion-specific antigens activate MCs, which prevent AAA healing and promote the production of more IgEs, leading to an amplification loop of the pathology.

Increased Local IgE Production in Allergic Rhinitis (AR) During Rhinovirus (RV) Infection

Increased Local IgE Production in Allergic Rhinitis (AR) During Rhinovirus (RV) Infection

A case report of combination of asthma and allergic rhinitis caused by local household sensitization with a brief analysis of literature

Currently diagnosis of allergic diseases is based largely on results of skin tests and laboratory methods of quantification of total and specific immunoglobulins E in serum in addition to clinical and instrumental data. However, in recent years it has been showed that systemic atopy is not always registered with these methods and specific immunoglobulins E may not have diagnostic concentrations in serum that makes it difficult to diagnose allergic diseases. The article presents a clinical case of combination of asthma and allergic rhinitis caused by local IgE production with normal level of serum I-4, reduced levels of IgG1, IgG2 and serum and secretory IgA in child aged 3 years.

IL-21 Is Increased in Nasal Polyposis and after Stimulation with Staphylococcus aureus Enterotoxin B

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease associated with lymphoid aggregates and local IgE production related to Staphylococcus aureus enterotoxins. T-follicular helper cells and their effector cytokine interleukin (IL)-21 play an important role in germinal center proliferation. Methods: IL-21 was determined on the mRNA level by qPCR in nasal tissue of 3 groups of patients: control (n = 17), chronic rhinosinusitis without nasal polyposis (CRSsNP; n = 23), and CRSwNP (n = 35). The expression of IL-21 by CD4+ T cells was analyzed in tissue at baseline and after 24-h stimulation of tissue fragments with S. aureus enterotoxin B (SEB) using flow cytometry. Finally, human nasal IL-21+CXCR5+CD4+ T cells were isolated and coincubated with human blood naive B cells to investigate their functionality. Results: IL-21 mRNA expression was increased in the CRSwNP group (p < 0.05) compared to the control group, and B-cell lymphoma-6 and B-lymphocyte-induced maturation protein-1 were upregulated in CRSwNP versus CRSsNP. Furthermore, SEB was able to increase IL-21 mRNA expression significantly (p < 0.01) in nasal polyps. Flow cytometry revealed that the source of IL-21 was predominantly CD4+ T cells and that IL-21+CD4+ T cells were significantly increased in polyp tissue and further increased after SEB stimulation. Finally, tissue CXCR5+CD4+ T cells derived from nasal polyp tissue were able to induce maturation of human naive B cells. Conclusions: IL-21- and IL-21-producing CD4+ T cells were increased in CRSwNP. In addition, SEB induced an increase in IL-21 and IL-21+CD4+ T cells, suggesting that S. aureus can modulate the function of Tfh cells in nasal polyps. We speculate that T-follicular helper cells and IL-21 are important in the pathophysiology of CRSwNP.