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

Genetic association of polymorphisms in the IL6R gene with severity of asthma, high levels of systemic sIL-6R and poor lung function has been reported (Hawkins et al. JACI 2012; 130:510-5). Higher levels of systemic IL-6 have been shown to be associated with asthma severity, elevated BMI, CRP and blood neutrophils (Peters et al. Lancet Respir Med 2016; 4:574-84). 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 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.