C5a Activates a Pro-Inflammatory Gene Expression Profile in Human Gaucher iPSC-Derived Macrophages. C5a Activates a Pro-Inflammatory Gene Expression Profile in Human Gaucher iPSC-Derived Macrophages

Gaucher disease (GD) is an autosomal recessive disorder caused by bi-allelic GBA1 mutations that reduce the activity of the lysosomal enzyme β-glucocerebrosidase (GCase). In the immune system, GCase deficiency deregulates signal transduction events, resulting in an inflammatory environment. It is known that the complement system promotes inflammation, and complement inhibitors are currently being considered as a novel therapy for GD; however, the mechanism by which complement drives ystemic macrophage-mediated inflammation remains incompletely understood. To help understand the mechanisms involved, we performed gene array analysis on rC5a-treated human control and GD-induced pluripotent stem cell (iPSC)-derived macrophages. Overall design: We analyzed gene expression changes from macrophages differentiated from iPSC lines derived from a patient with type 2 Gaucher disease or healthy controls treated with rC5a using the Affymetrix Clariom S human assay.