Anna Knauer

Impact of glycosylation on IgG4-induced signaling in neutrophils 

A key step in the pathogenesis of epidermolysis bullosa acquisita (EBA) is the development of anti-hCOL7 antibodies directed against collagen type VII, which serves as an anchor fibril between the epidermis and the dermis. Activation of neutrophils by COL7/anti-hCOL7 immunocomplexes lead to complement activation and reactive oxygen species (ROS) release, resulting in split formation at the dermal-epidermal junction. This becomes visible as blistering of the skin.Pathogenicity of autoantibodies depends on the antibody subclass. Within the same subclass, cellular functions and inflammatory activity of the neutrophils are determined by the sugar moiety attached to the antibodies. In my project, I will investigate the kinome signature in neutrophils activated by differentially glycosylated IgG4 immunocomplexes. Furthermore, I will determine specific kinase activity by measuring the phosphorylation of kinases by Western blot. The most important cellular function will be the release of ROS, which will be measured by a luminescence-based assay.