Impact of glycosylation on IgG3-induced signaling in neutrophiles

Epidermolysis bullosa aquisita (EBA) is an autoimmune, subepidermal blistering disease which belongs to the group of pemphigoid diseases. The underlying pathomechanism is the binding of autoantibodies (mainly IgG) to collagen type VII, a major component of the anchoring fibrils of the dermal-epidermal junction (DEJ). The formation of the immune complex (IC) leads to activation of immune cells, especially neutrophils resulting in the release of reactive oxygen species (ROS) and proteases. This directly contributes to split formation in the DEJ. Importantly, not all ICs activate the neutrophils in the same way. The affinity is modulated by subclass and glycosylation pattern of the IgG antibodies. 

Therefore, the overarching goal of the project is to identify kinase signatures and cellular functions in neutrophils activated with different IgG subclasses containing different glycoforms. Specifically, my project aims to investigate the function of differentially glycosylated IgG3 ICs.