Anti-FCER2 (aa 48-321) polyclonal antibody

Background: A growing number of severe Mycoplasma pneumoniae pneumonia (MPP) cases have been reported recently. However, the pathogenesis of severe MPP is not clear. In the current study, transcriptome sequencing was used to identify gene expression and alternative splicing profiles to provide insights into the pathogenesis of severe MPP. Methods: RNAs of bronchoalveolar lavage fluid (BALF) samples from three severe MPP children and three mild MPP children were analyzed respectively by deep sequencing followed by computational annotation and quantification. Results: The gene expression analysis revealed 14 up-regulated and 34 down-regulated genes in severe MPP children comparing to mild MPP children. The top 10 most up-regulated genes were IGHV1-69, CH17-472G23.1, ATP1B2, FCER2, MUC21, IL13, FCRLB, CLEC5A, FAM124A, and INHBA. The top 10 most down-regulated genes were OSTN-AS1, IL22RA2, COL3A1, C1orf141, IGKV2-29, RP11-731F5.2, IGHV4-4, KIRREL, DNASE1L3, and COL6A2. Clustering analysis revealed similar expression pattern of CLEC5A, IL13, FCER2, and FLT1. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed changes related to primary immunodeficiency in severe MPP children comparing to mild MPP children; the pathway involves CD19, TNFRSF13C, CD79A, and AICDA genes. Among the differentially expressed genes, significant alternative splicing events were found in FCER2 and FCRLA. Conclusions: The current study on RNA sequencing provides novel insights into the pathogenesis of severe MPP in terms of gene expression and alternative splicing. The up-regulation of IL13, FCER2, FLT1, and CLEC5A and the down-regulation of CD79A, AICDA, CD19, and TNFRSF13C may contribute to the pathogenesis of severe MPP. The differential expressions of FCER2 and FCRLA could be due to their alternative splicing.

BackgroundThe clinical response to inhaled corticosteroids (ICS) is associated with single nucleotide polymorphisms (SNPs) in various genes. This study aimed to relate variations in genes in the steroid pathway and asthma susceptibility genes to exacerbations in children and young adults treated with ICS. MethodsWe performed a meta-analysis of three cohort studies: Pharmacogenetics of Asthma Medication in Children: Medication with Anti-Inflammatory effects (n=357, age: 4-12years, the Netherlands), BREATHE (n=820, age: 3-22years, UK) and Paediatric Asthma Gene Environment Study (n=391, age: 2-16years, UK). Seventeen genes were selected based on a role in the glucocorticoid signalling pathway or a reported association with asthma. Two outcome parameters were used to reflect exacerbations: hospital visits and oral corticosteroid (OCS) use in the previous year. The most significant associations were tested in three independent validation cohorts; the Childhood Asthma Management Programme (clinical trial, n=172, age: 5-12years, USA), the Genes- environment and Mixture in Latino Americans II- study (n=745, age: 8-21, USA) and the Pharmacogenetics of adrenal suppression cohort (n=391, age: 5-18, UK) to test the robustness of the findings. Finally, all results were meta-analysed. ResultsTwo SNPs in ST13 (rs138335 and rs138337), but not in the other genes, were associated at a nominal level with an increased risk of exacerbations in asthmatics using ICS in the three cohorts studied. In a meta-analysis of all six studies, ST13 rs138335 remained associated with an increased risk of asthma-related hospital visits and OCS use in the previous year; OR=1.22 (P=0.013) and OR=1.22 (P=0.0017), respectively. Conclusion and clinical relevanceA novel susceptibility gene, ST13, coding for a cochaperone of the glucocorticoid receptor, is associated with exacerbations in asthmatic children and young adults despite their ICS use. Genetic variation in the glucocorticoid signalling pathway may contribute to the interindividual variability in clinical response to ICS treatment in children and young adults.