National Jewish Health

About: National Jewish Health is a healthcare organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: T cell & Asthma. The organization has 883 authors who have published 833 publications receiving 79201 citations. The organization is also known as: National Jewish Medical and Research Center.

Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency

Abstract: Background Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that causes early onset pulmonary emphysema and airways obstruction. The complete mechanisms via which AATD causes lung disease are not fully understood. To improve our understanding of the pathogenesis of AATD, we investigated gene expression profiles of bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMCs) in AATD individuals. Methods We performed RNA-Seq on RNA extracted from matched BAL and PBMC samples isolated from 89 subjects enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Subjects were stratified by genotype and augmentation therapy. Supervised and unsupervised differential gene expression analyses were performed using Weighted Gene Co-expression Network Analysis (WGCNA) to identify gene profiles associated with subjects’ clinical variables. The genes in the most significant WGCNA module were used to cluster AATD individuals. Gene validation was performed by NanoString nCounter Gene Expression Assay. Result We observed modest effects of AATD genotype and augmentation therapy on gene expression. When WGCNA was applied to BAL transcriptome, one gene module, ME31 (2312 genes), correlated with the highest number of clinical variables and was functionally enriched with numerous immune T-lymphocyte related pathways. This gene module identified two distinct clusters of AATD individuals with different disease severity and distinct PBMC gene expression patterns. Conclusions We successfully identified novel clusters of AATD individuals where severity correlated with increased immune response independent of individuals’ genotype and augmentation therapy. These findings may suggest the presence of previously unrecognised disease endotypes in AATD that associate with T-lymphocyte immunity and disease severity.

Methods for detection of respiratory diseases

Abstract: Disclosed are methods of identifying, predicting and treating subjects at risk for exacerbation or the presence of a respiratory disease, by detecting expression levels of one or more proteins associated with the respiratory disease, wherein said one or more proteins is selected from the group of CCL24, IL2RA, APOA4, GC, IgA, LPA, KLK3 F, FAS, NRCAM, TNFRSFIOC, IL12B, IL23A, RAGE, CCL20, ICAM1, SERPINA7, CDH13 and CDH1, and wherein said respiratory disease may be chronic obstructive pulmonary disease or emphysema.