IgD+IgM- B Cells in Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is the most frequent form of primary hypogammaglobulinemia in adults. In addition to recurrent infections and respiratory manifestations, CVID patients may present several non-infection complications such as autoimmune diseases. The mechanisms that lead to immune dysregulation in CVID are not completely understood. Given the role of IgD on naïve B cells in the maintenance of tolerance and secreted IgD in the respiratory mucosa, we evaluated the frequency of IgD+ naïve and IgD+ memory B cells in CVID patients. Here, no differences were observed in the percentages and proliferative responses of anergic IgD+IgM-CD27- B cells between CVID patients, with or without autoimmune disease, and the control group. Interestingly, in the compartment of memory B cells, the percentage of IgD+IgM- cells was higher only in CVID patients with allergic rhinitis/allergic asthma. Our results may indicate that anergic IgD+IgM-CD27- B cells may not be compromised in our CVID cohort. However, IgD+IgM- memory B cells may play a role in the immunopathogenesis of allergic rhinitis/allergic asthma in CVID patients. Further studies are needed to better understand the participation of IgD+IgM- memory B cells in the immunopathogenesis of allergic rhinitis/allergic asthma in CVID patients.

Microenvironment modulation by key regulators of RNA N6-methyladenosine modification in respiratory allergic diseases.

BACKGROUND: RNA N6-methyladenosine (m6A) regulators are considered post-transcriptional regulators that affect several biological functions, and their role in immunity, in particular, is emerging. However, the role of m6A regulators in respiratory allergic diseases remains unclear. Therefore, we aimed to investigate the role of key m6A regulators in mediating respiratory allergic diseases and immune microenvironment infiltration characteristics. METHODS: We downloaded gene expression profiles of respiratory allergies from the Gene Expression Omnibus (GEO) database and we performed hierarchical clustering, difference analysis, and construction of predictive models to identify hub m6A regulators that affect respiratory allergies. Next, we investigate the underlying biological mechanisms of key m6A regulators by performing PPI network analysis, functional enrichment analysis, and immune microenvironment infiltration analysis. In addition, we performed a drug sensitivity analysis on the key m6A regulator, hoping to be able to provide some implications for clinical medication. RESULTS: In this study, we identified four hub m6A regulators that affect the respiratory allergy and investigated the underlying biological mechanisms. In addition, studies on the characteristics of immune microenvironment infiltration revealed that the expression of METTL14, METTL16, and RBM15B correlated with the infiltration of the mast and Th2 cells in respiratory allergy, and METTL16 expression was found to be significantly negatively correlated with macrophages for the first time (R = -0.53, P < 0.01). Finally, a key m6A regulator, METTL14, was screened by combining multiple algorithms. In addition, by performing a drug sensitivity analysis on METTL14, we hypothesized that it may play an important role in the improvement of allergic symptoms in the upper and lower airways with topical nasal glucocorticoids. CONCLUSIONS: Our findings suggest that m6A regulators, particularly METTL14, play a crucial role in the development of respiratory allergic diseases and the infiltration of immune cells. These results may provide insight into the mechanism of action of methylprednisolone in treating respiratory allergic diseases.

Heat shock cognate 70 protein like-2 protein in camphor pollen is one of the major culprits of asthma.

AIMS: In recent decades, Cinnamomum camphora have gradually become the main street trees in Shanghai. This study aims to investigate the allergenicity of camphor pollen. MAIN METHODS: A total of 194 serum samples from patients with respiratory allergy were collected and analyzed. Through protein profile identification and bioinformatics analysis, we hypothesized that heat shock cognate protein 2-like protein (HSC70L2) is the major potential allergenic protein in camphor pollen. Recombinant HSC70L2 (rHSC70L2) was expressed and purified, and a mouse model of camphor pollen allergy was established by subcutaneous injection of total camphor pollen protein extract (CPPE) and rHSC70L2. KEY FINDINGS: Specific IgE was found in the serum of 5 patients in response to camphor pollen and three positive bands were identified by Western blotting. Enzyme-linked immunosorbent assay (ELISA), Immune dot blot and Western blot experiments confirmed that CPPE and rHSC70L2 can cause allergies in mice. Moreover, rHSC70L2 induces polarization of peripheral blood CD4+ T cells to Th2 cells in patients with respiratory allergies and mice with camphor pollen allergy. Finally, we predicted the T cell epitope of the HSC70L2 protein, and through the mouse spleen T cell stimulation experiment, we found that the 295EGIDFYSTITRARFE309 peptide induced T cells differentiation to Th2 and macrophages differentiation to the alternatively activated (M2) state. Moreover, 295EGIDFYSTITRARFE309 peptide increased the serum IgE levels in mice. SIGNIFICANCE: The identification of HSC70L2 protein can provide novel diagnostic and therapeutic targets for allergies caused by camphor pollen.

The impact of adiposity indices on lung function in children with respiratory allergic diseases.

INTRODUCTION: The effect of obesity on lung function in children stratified by asthma status is not fully elucidated. We evaluated the impact of adiposity indices, including Body Mass Index (BMI) and estimated fat mass (eFT), on lung changes in asthmatic and non-asthmatic children with rhinitis. PATIENTS AND METHODS: We performed a retrospective review of 400 pediatric patients, classified into an asthma group (n = 200) and a no-asthma group (n = 200). According to the BMI z-score all subjects were classified into normal-weight patients (NW; -2 ≤ BMI z-score <1) and overweight patients/patients with obesity (OW/OB; BMI z-score ≥1). Lung function parameters were measured by spirometry. BMI and eFM were considered as adiposity indices. RESULTS: Excess weight/obesity was present in 37 % of patients. The OW/OB group showed higher basal forced expiratory vital capacity (FVC) and lower forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio compared to the NW group (p ≤ 0.01). FVC and FEV1 were correlated with the BMI z-score, and FEV1/FVC with eFT (p ≤ 0.01). No differences were noted between the NW and the OW/OB groups in terms of respiratory parameters except for FVC (p < 0.01). In the OW/OB group, asthma patients were significantly different based on FEV1, FEV1/FVC, and forced expiratory flow at 25-75 % of FVC (FEF25/75) (p < 0.01). The BMI z-score was correlated with FVC and FEV1 in both the no-asthma and asthma groups (p ≤ 0.01 and p ≤ 0.05, respectively), while eFM was correlated with FEV1/FVC (p = 0.007) in the asthma group only. CONCLUSION: Obesity seems to have a significant impact on lung function in children with respiratory allergic diseases. BMI and eFM may be used to evaluate the impact of adiposity on lung function.

Distribution characteristics of cow's milk-sIgE components in children with respiratory allergic diseases in southern China.

BACKGROUND: Cow's milk (CM) is the main food allergen for toddlers and infants. Presently, studies on CM specific immunoglobulin E (sIgE) sensitization and positive distribution of CM components ALA-, CAS-, and BLG-sIgE are lacking in infants with respiratory allergic diseases, especially in southern China. This study therefore aimed to investigate the distribution of CM sensitization and the relation between its components α-lactalbumin (ALA), ß-lactoglobulin (BLG) and casein (CAS) sIgE in children with respiratory allergic diseases in southern China. METHODS: A total of 1839 children (≤12 years) with respiratory diseases and detected CM-sIgE levels were included. Serum samples were collected from the Respiratory Diseases Bioresources Center of the National Center for Respiratory Diseases in southern China from August 2012 to July 2017. ALA-, BLG-, and CAS-sIgE were detected and questionnaires were completed in 103 children. RESULTS: A total of 36.7% children were positive for CM-sIgE. CM-sIgE levels were higher in asthmatic bronchitis (AB) group than in other allergic respiratory disease groups (all P < 0.05). Among the 103 CM-sIgE-sensitized children, 64.08% had a history of family allergies. There were 84.47% of the children who tested positive for two or more sIgE components. The average ALA-, BLG-, and CAS-sIgE levels were 1.91 kU/L, 1.81 kU/L, and 0.62 kU/L, respectively. The CM-sIgE level showed a correlation with BLG-sIgE (rs = 0.833), ALA-sIgE (rs = 0.816), and CAS-sIgE (rs = 0.573) levels (all p < 0.001). CONCLUSIONS: In southern China, CM-sIgE levels were higher in children with AB than in those with other respiratory allergic diseases. ALA and BLG were the main allergenic components detected in CM-sIgE-sensitized children with respiratory allergic diseases.

Climate change and respiratory allergic diseases

There is a firm consensus that Earth's climate has been changed and will be changed in further future due to increasing greenhouse gas emissions. Climate change affects human health and respiratory allergic diseases, such as asthma and allergic rhinitis, in various ways. The increase in both the incidence of asthma and global surface temperature in the same period suggests that climate change is a plausible explanation for the asthma epidemic. Additionally, climate change could influence also the severity and acute exacerbation of asthma. Several mechanisms were suggested to explain the effects of climate change on respiratory allergic diseases: increased exposure to pollens and molds spores, aggravated air pollutions, direct effects of extreme weather and thunderstorm and changes in respiratory infections. However, data and evidences are lacking to answer what the net effects of climate on asthma and allergic rhinitis and its mechanisms are. Great efforts and active roles are required for the physicians in developing strategies to mitigate climate change and adaptation to its effects on respiratory allergic diseases.

A comparison of Sensitization to Major Indoor & Outdoor Inhalant Allergens in Children with Respiratory Allergic Diseases / 소아알레르기및호흡기학회지

PURPOSE: It has been shown that the sensitization to inhalant allergens on the development of asthma or rhinitis in childhood is related to hereditary disposition and environmental factors. This study was conducted to compare the degree of sensitization to major inhalant allergens in bronchial asthma and rhinitis and to find factors which have an effect on it. METHODS: Skin prick tests were done on the 410 atopic bronchial asthma and rhinitis patients who visited the pediatric allergy clinic from January 1987 through December 1996. We divided the patients into 3 groups: an indoor allergen group sensitive to D.p., D.f., cat fur, dog hair and cockroach; an outdoor allergen group to tree pollen, ragweed pollen, and grass pollen; and a group to both indoor and oudoor allegens. RESULTS: 1) Based on their ages, the prevalence of sensitization was relatively high in 5-6 years old, to indoor allergen and in 11-12 years old to the outdoor allergen. 2) Among the subjects sensitized only to indoor allergens, 34.2% had asthma. 6.7% had rhinitis, and 59.1% both diagnoses. For those sensitized only to outdoor allergens, these values were respectively 29.0%, 48.4% and 22.6%, respectively. 3) The prevalence of indoor allergen sensitization was significantly high in children, living in house, in urban areas, and having carpet/sofa/bed at home(P<0.05). CONCLUSIONS: The younger age group showed more sensitization to indoor allergens than to outdoor allergens. The indoor allergens were strongly related to asthma and the outdoor ones to rhinitis. As a result, it seems that it is very helpful for a prevention of asthma in childhood to take an early environmental control for inhalant allergens.