Abstract
Background: TNFAIP3 is a ubiquitin-modifying enzyme that attenuates NF-kB activation and is reported to be suppressed in epithelial cultures of severe asthma patients (Schuijs MJ et al., Science 2015).
Aims & Objectives: To investigate TNFAIP3 gene expression in bronchial brushings and sputum cells in subjects from the U-BIOPRED consortium.
Methods: We used gene expression analysis to study TNFAIP3 expression in bronchial biopsies (n=108), bronchial brushings (n=147) and sputum (n=120), from healthy controls (HC), mild moderate asthmatics (MMA) and severe asthmatics who were smokers (SAsm) or non-smokers (SAn) in the U-BIOPRED cohort.
Results: There was no change in TNFAIP3 expression in bronchial biopsies or bronchial brushings between any of the subject groups. In contrast TNFAIP3 expression was significantly increased in sputum cells from SA patients, 1.6-fold between SAn and HC and 2.3-fold between SAn and MMA. Differences were greater when subjects were grouped according to sputum granulocytes. Neutrophilic and mixed granulocyte asthmatics expressed the highest levels of TNFAIP3 with a 3.8-fold increase seen between neutrophilic and paucigranulocytic asthmatics (FDR<10-6).
Conclusion: TNFAIP3 expression is not reduced in bronchial biopsies in asthma but is markedly elevated in SAn and particularly in those with neutrophilic asthma. Further analysis of ubiquitin and de-ubiquitinating enzymes in severe asthma is required.
EU-IMI Funded
- Copyright ©the authors 2016
