A hypothesis driven approach investigating the interleukin-6 pathway in UBIOPRED severe asthma patients

In this study, we investigated whether sputum IL-6 pathway activity is aberrant in a subgroup of asthma patients and is associated with particular clinical characteristics. We used a hypothesis driven analysis by investigating sputum transcriptomics (n=77), sputum and blood proteomics and clinical data from UBIOPRED consortium severe asthma cohort. As asthma is a heterogeneous disease, we used a clustering approach to identify subgroups of patients using genes correlated with IL6R sputum mRNA.The analysis identified two subgroups with high (n=33) and low (n=28) IL6R expression. Mean IL6R expression level in the high IL6R group was 2.8-fold (p<0.001) higher than the low group and 3.5-fold (p<0.001) higher than the level in healthy controls. The high IL6R group had significantly higher sputum neutrophil percentages (76%) compared with low IL6R patients (42%). These patients also have significantly worse lung function post-bronchodilator and higher levels of serum CRP (3.1 fold, p<0.002). There were no significant differences in percentages of sputum and blood eosinophils, ACQ, FENO, BMI, smoking history and medication between the two groups.This IL6R-high sub-population of severe asthma patients with high sputum neutrophilia has a high unmet need that could potentially benefit from targeting IL-6 pathway.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Molecular Pathology and Functional Genomics Source Type: research