Characterization of CD4-endotypes in severe allergic asthma for future precision medicine

Asthma is a heterogenous disease. The selection of the best treatment for symptom control is a challenge. The development of predictive biomarker assays is needed that combine gene expression and immune response data to enable patient selection for targeted therapy. Aims: To identify the cytokine profiles of CD4+cells and molecular signatures of whole blood (WB) in clinically defined patients with severe allergic asthma that are predictive of therapy responses. Methods: CD4 + cells were isolated from WB of patients with severe allergic asthma (n=10) and healthy donors (n=10). They were stimulated ex vivo with Ionomycin (IO)/PMA. The effect of an IgE antibody (Omalizumab (OMA)) incubation (25 to 100µg/ml) was determined in vitro. Cytokines were measured in serum and in supernatants of unstimulated and stimulated (20hrs) CD4 + cells (10 5 ) by ELISA. Gene expression profiles of cytokines were determined in WB by RTqPCR. Results: Patients’ clinical characteristics were: (mean) FEV1(%) 59.8%; IgE 469IU/ml; EOS 508/µl; FENO 84.7 ppb; ACQ 11.5. IO/PMA induced a higher cytokine release (IL-4, IL-5, IL-13, TNF-α) of asthma CD4 + cells (4f, 813f, 271f, 16f) compared to healthy donors (3f; 8f, 6.8f, 16f)(p Conclusion: First evidences of CD4+-endotypes including gene expression data suggest predictive value for the clinical response to biologicals. Different cytokine profiles and responses underline the heterogeneity of asthma.