Type 2 Cytokines and Biomarkers in Asthma Patient Sera Show Coordinated Expression and Identify Patient Subsets

Severe asthma occurs in ~10% of asthma patients and is difficult to treat. New drugs are in development that target components of the Type 2 inflammatory pathway. Further defining the expression profile of Type 2 inflammatory components may help identify patients likely to benefit from these new treatments. We hypothesised that i) several Type 2 biomarkers are in the same mechanistic effector pathway and would show coordinated expression levels in asthma patient sera, ii) the expression profile of these biomarkers may identify a subset of asthma patients likely to benefit from drugs targeting the Type 2 inflammatory pathway. To test this hypothesis we utilised the Genetics of Asthma Severity & Phenotypes (GASP) cohort1. IL33, TSLP, ST2, IL13, IL5, IL6 & Periostin serum levels were measured in 196 asthmatics by Luminex. Data identified that the expression of many of the biomarkers were significantly correlated with each other, e.g. TSLP & IL5 (R2:0.52, P<0.0001), TSLP & IL33 (R2:0.53, P<0.0001). Additionally, soluble ST2 levels were higher & TSLP lower in severe asthma compared to mild asthma (P=0.0004 and P=0.0024 respectively). These data suggest Type 2 biomarkers demonstrate some coordinated expression; consequently combination therapy could potentially be useful for some asthma patients with elevated levels of multiple drivers of Type 2 inflammation. Similarly, blood biomarkers may identify more severe asthma patients as a target population for anti-TSLP & anti-ST2. Ongoing studies aim to replicate these findings & determine the contribution of genetic variants1 to drive the expression of these Type 2 biomarkers. 1Shrine et al; 2019 Lancet Respir Med. 2019 Jan;7(1):20-34