Immunological and genetic aspects of asthma and allergy

Prevalence of allergy and allergic asthma are increasing worldwide. More than half of the US population has a positive skin prick test and approximately 10% are asthmatics. Many studies have been conducted to define immunological pathways underlying allergy and asthma development and to identify the main genetic determinants. In the effort to find missing pieces of the puzzle, new genomic approaches and more standardized ones, such as the candidate gene approach, have been used collectively. This article proposes an overview of the actual knowledge about immunological and genetic aspects of allergy and asthma. Special attention has been drawn to the challenges linked to genetic research in complex traits such as asthma and to the contribution of new genomic approaches

Association study of genes associated to asthma in a specific environment, in an asthma familial collection located in a rural area influenced by different industries

Eight candidate genes selected in this study were previously associated with gene-environment interactions in asthma in an urban area. These genes were analyzed in a familial collection from a founder and remote population (Saguenay–Lac-Saint-Jean; SLSJ) located in an area with low air levels of ozone but with localized areas of relatively high air pollutant levels, such as sulphur dioxide, when compared to many urban areas. Polymorphisms (SNPs) were extracted from the genome-wide association study (GWAS) performed on the SLSJ familial collection. A transmission disequilibrium test (TDT) was performed using the entire family sample (1,428 individuals in 254 nuclear families). Stratification according to the proximity of aluminium, pulp and paper industries was also analyzed. Two genes were associated with asthma in the entire sample before correction (CAT and NQO1) and one was associated after correction for multiple analyses (CAT). Two genes were associated when subjects were stratified according to the proximity of aluminium industries (CAT and NQO1) and one according to the proximity of pulp and paper industries (GSTP1). However, none of them resisted correction for multiple analyses. Given that the spatial pattern of environmental exposures can be complex and inadequately represented by a few stationary monitors and that exposures can also come from sources other than the standard outdoor air pollution (e.g., indoor air, occupation, residential wood smoke), a new approach and new tools are required to measure specific and individual pollutant exposures in order to estimate the real impact of gene-environment interactions on respiratory health

From expression pattern to genetic association in asthma and asthma-related phenotypes

Background : Asthma is a complex disease characterized by hyperresponsiveness, obstruction and inflammation of the airways. To date, several studies using different approaches as candidate genes approach, genome wide association studies, linkage analysis and genomic expression leaded to the identification of over 300 genes involved in asthma pathophysiology. Combining results from two studies of genomic expression, this study aims to perform an association analysis between genes differently expressed in bronchial biopsies of asthmatics compared to controls and asthma-related phenotypes using the same French-Canadian Caucasian population. Results : Before correction, 31 of the 85 genes selected were associated with at least one asthma-related phenotype. We found four genes that survived the correction for multiple testing. The rs11630178 in aggrecan gene (AGC1) is associated with atopy (p=0.0003) and atopic asthma (p=0.0001), the rs1247653 in the interferon alpha-inducible protein 6 (IFI6), the rs1119529 in adrenergic, alpha-2A-, receptor (ADRA2A) and the rs13103321 in the alcohol dehydrogenase 1B (class I), beta polypeptide (ADH1B), are associated with asthma (p=0.019; 0.01 and 0.002 respectively). Conclusion : To our knowledge, this is the first time those genes are associated with asthma and related traits. Consequently, our study confirms that genetic and expression studies are complementary to identify new candidate genes and to investigate their role to improve the comprehension of the complexity of asthma pathophysiology

Could the epigenetics of eosinophils in asthma and allergy solve parts of the puzzle?

Epigenetics is a field of study investigating changes in gene expression that do not alter the DNA sequence. These changes are often influenced by environmental or social factors and are reversible. Epigenetic mechanisms include DNA methylation, histone modification, and noncoding RNA. Understanding the role of these epigenetic mechanisms in human diseases provides useful information with regard to disease severity and development. Several studies have searched for the epigenetic mechanisms that regulate allergies and asthma; however, only few studies have used samples of eosinophil, a proinflammatory cell type known to be largely recruited during allergic or asthmatic inflammation. Such studies would enable us to better understand the factors that influence the massive recruitment of eosinophils during allergic and asthmatic symptoms. In this review, we sought to summarize different studies that aimed to discover differential patterns of histone modifications, DNA methylation, and noncoding RNAs in eosinophil samples of individuals with certain diseases, with a particular focus on those with asthma or allergic diseases

Combining omics data to identify genes associated with allergic rhinitis

Allergic rhinitis is a common chronic disorder characterized by immunoglobulin E-mediated inflammation. To identify new genes associated with this trait, we performed genome- and epigenome-wide association studies and linked marginally significant CpGs located in genes or its promoter and SNPs located 1 Mb from the CpGs, by identifying cis methylation quantitative trait loci (mQTL). This approach relies on functional cellular aspects rather than stringent statistical correction. We were able to identify one gene with significant cis-mQTL for allergic rhinitis, caudal-type homeobox 1 (CDX1). We also identified 11 genes with marginally significant cis-mQTLs (p < 0.05) including one with both allergic rhinitis with or without asthma (RNF39). Moreover, most SNPs identified were not located closest to the gene they were linked to through cis-mQTLs counting the one linked to CDX1 located in a gene previously associated with asthma and atopic dermatitis. By combining omics data, we were able to identify new genes associated with allergic rhinitis and better assess the genes linked to associated SNPs

The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a review of the current global status

There is currently an ongoing worldwide pandemic of a novel virus belonging to the family of Coronaviruses (CoVs) which are large, enveloped, plus-stranded RNA viruses. Coronaviruses belong to the order of Nidovirales, family of Coronavirinae and are divided into four genera: alphacoronavirus, betacoronavirus, gammacoronavirus and deltacoronavirus. CoVs cause diseases in a wide variety of birds and mammals and have been found in humans since 1960. To date, seven human CoVs were identified including the alpha-CoVs HCoVs-NL63 and HCoVs-229E and the beta-CoVs HCoVs-OC43, HCoVs-HKU1, the severe acute respiratory syndrome-CoV (SARS-CoV), the Middle East respiratory syndrome-CoV (MERS-CoV) and the novel virus that first appeared in December 2019 in Wuhan, China, and rapidly spread to 213 countries as of the writing this paper. It was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the international committee on taxonomy of viruses (ICTV) and the disease's name is COVID-19 for coronavirus disease 2019. SARS-CoV-2 is very contagious and is capable of spreading from human to human. Infection routes include droplet and contact, and aerosol transmission is currently under investigation. It is associated with a respiratory illness that may cause severe pneumonia and acute respiratory distress syndrome (ARDS). SARS-CoV-2 became an emergency of international concern. As of July 12, 2020, the virus has been responsible for 12,698,995 confirmed cases and 564,924 deaths worldwide and the number is still increasing. Up until now, no specific treatment has yet been proven effective against SARS-CoV-2. Since the beginning of this outbreak, several interesting papers on SARS-CoV-2 and COVID-19 have been published to report on the phylogenetic evolution, epidemiology, pathogenesis, transmission as well as clinical characteristics of COVID-19 and possible treatments agents. This paper is a systematic review of the available literature on SARS-CoV-2. It was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and aims to help readers access the latest knowledge surrounding this new infectious disease and to provide a reference for future studies

First steps of asthma management with a personalized ontology model

Asthma is a chronic respiratory disease characterized by severe inflammation of the bronchial mucosa. Allergic asthma is the most common form of this health issue. Asthma is classified into allergic and non-allergic asthma, and it can be triggered by several factors such as indoor and outdoor allergens, air pollution, weather conditions, tobacco smoke, and food allergens, as well as other factors. Asthma symptoms differ in their frequency and severity since each patient reacts differently to these triggers. Formal knowledge is selected as one of the most promising solutions to deal with these challenges. This paper presents a new personalized approach to manage asthma. An ontology-driven model supported by Semantic Web Rule Language (SWRL) medical rules is proposed to provide personalized care for an asthma patient by identifying the risk factors and the development of possible exacerbations

Cell-specific DNA methylation signatures in asthma

Asthma is a complex trait, often associated with atopy. The genetic contribution has been evidenced by familial occurrence. Genome-wide association studies allowed for associating numerous genes with asthma, as well as identifying new loci that have a minor contribution to its phenotype. Considering the role of environmental exposure on asthma development, an increasing amount of literature has been published on epigenetic modifications associated with this pathology and especially on DNA methylation, in an attempt to better understand its missing heritability. These studies have been conducted in different tissues, but mainly in blood or its peripheral mononuclear cells. However, there is growing evidence that epigenetic changes that occur in one cell type cannot be directly translated into another one. In this review, we compare alterations in DNA methylation from different cells of the immune system and of the respiratory tract. The cell types in which data are obtained influences the global status of alteration of DNA methylation in asthmatic individuals compared to control (an increased or a decreased DNA methylation). Given that several genes were cell-type-specific, there is a great need for comparative studies on DNA methylation from different cells, but from the same individuals in order to better understand the role of epigenetics in asthma pathophysiology

Functional classes of bronchial mucosa genes that are differentially expressed in asthma

BACKGROUND: Asthma pathogenesis and susceptibility involves a complex interplay between genetic and environmental factors. Their interaction modulates the airway inflammation and remodelling processes that are present even in mild asthma and governs the appearance and severity of symptoms of airway hyperresponsiveness. While asthma is felt to develop as the result of interaction among many different genes and signalling pathways, only a few genes have been linked to an increased risk of developing this condition. RESULTS: We report the results of expression microarray studies using tissue obtained from bronchial biopsies of healthy controls and of subjects with allergic asthma, both before and following inhaled corticotherapy. We identified 79 genes that show significant differences in expression (following Bonferroni cutoff using p < 6.6 × 10(-6 )to correct for multiple testing) in asthmatics compared to controls at significance levels. These included 21 genes previously implicated in asthma, such as NOS2A and GPX3, as well as new potential candidates, such as ALOX15, CTSC and CX3CR1. The expression levels of one third of these transcripts were partially or completely corrected following inhaled corticosteroid therapy. CONCLUSION: The study shows that bronchial biopsies obtained from healthy and asthmatic subjects display distinct expression profiles. These differences provide a global view of physiopathologic processes active in the asthmatic lung and may provide invaluable help to clarify the natural history of asthma