Association of complement pathway activation with severe eosinophilic asthma in the C-BIOPRED asthma cohort

Background: There is evidence of complement activation in asthma but its role remains unclear. Objective: To analyze the level of complement proteins in sputum by proteomics assay in the Chinese asthma cohort (C-BIOPRED). Method: Weighted gene correlation network analysis was used to define the unique modules that are highly correlated with clinical, physiologic and inflammatory traits. Results: A brown module was positive associated with blood eosinophil percentage (rho=0.38), blood eosinophil counts (rho=0.39), FeNO (rho=0.31), exacerbations (rho=0.13) and sputum eosinophil (%) (rho=0.48).The top enriched pathway of the brown module was complement and coagulation cascades.C5 and the C5 downstream proteins C6, C7, C8B, C8G and C9 were significantly up-regulated in the eosinophil-high group (sputum eosinophil % ≥ 2%). As a validation, sputum C5 and C9 levels were also up-regulated in the severe asthma U-BIOPRED eosinophil-high groups. Conclusion: Complement factors are highly expressed in and correlate with eosinophilic inflammation, supporting a role for the complement cascade in severe eosinophilic asthma.