TP A5: The relevance of the C5a/C5aR1 axis for induction of autoantibody response in epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease caused by auto-antibodies against collagen VII (ColVII), an anchoring fibril in the skin.Such antibodies induce an inflammatory cascade eventually resulting in the generation of C5a, which recruits and activates neutrophils. Such neutrophils secrete proteolytic enzymes which lead to dermal-epidermal separation and blister formation. Previously, we found that C5a receptor 1 (C5aR1) deficiency protects from skin blistering in a passive model of EBA.

This finding demonstrates a critical role for C5aR1 in the effector phase of the autoimmune disease. The role of the C5a/C5aR1 axis and its cross-talk with Fc-gamma receptors for disease initiation, that is the formation of pathogenic antibodies in an active model of EBA, was at this time point still unclear.

However, recently we have shown that also in the antibody transfer model of EBAthat C5aR1 deficiency protects from disease development due to the production of less pathogenic antibodies, suggesting that C5aR1 is not only protecting from disease during the effector phase but is also critical for the creation of pathogenic auto-Abs in the initiation phase.