The fraction of circulating type 2 innate lymphoid cells in peripheral blood is associated with asthma severity

<b>Background:</b> The mechanisms driving inflammation in severe asthma are not fully understood. Experimental studies have suggested type 2 innate lymphoid cells (ILC2) as a potential driver of severe steroid-refractory eosinophilic asthma by release of type 2 cytokines through a non-Th2-mediated innate immune response. <b>Aim:</b> We aimed to examine the association between the fraction of ILC2s in peripheral blood and asthma severity. <b>Methods:</b> A total of n=18 patients with mild-moderate and n=21 patients with severe asthma (according to ERS/ATS guidelines) were recruited and grouped based on asthma severity. Data on atopy, lung function, ICS dose, blood and sputum differential counts and FeNO was obtained. Circulating ILC2s (Lin−CD45+CD127+CRTH2+) were quantified using fluorescence-activated cell sorting. <b>Results:</b> Sex (50.0% vs. 42.9% female) and age (mean±SD 45.5±15.2 vs. 51.6±13.7 years)) did not differ between groups. Median daily dose of budesonide was 800 ug (min 400-max 1200) vs. 1600 ug (min 1600-max 3200). A significantly higher fraction of circulating ILC2 cells was detected in the blood of patients with severe asthma compared to mild-moderate asthma (Mann-Whitney U test; p = 0.0004). In a multiple linear regression model adjusting for asthma severity, sex, age, blood and sputum eosinophilia, FeNO, smoking and atopy, the difference in ILC2 fraction was 44% attributable to asthma severity (p=0.007); no other variables were significant. <b>Conclusions:</b> In this stable asthma cohort, the fraction of ILC2 cells in peripheral blood was strongly associated with asthma severity, independently of other inflammatory markers. Further analyses to identify the pathways involved are ongoing.