Epidermolysis bullosa acquisita (EBA) is a prototypic autoantibody-mediated disease, defined by immunoglobulin G (IgG) autoantibodies (Aab) targeting type VII collagen (COLVII) within the anchoring fibrils of the dermal-epidermal junction (DEJ). Upon antigen binding these Aab initiate disease progression and tissue destruction via Fc-mediated effector functions. Both, the activation of the complement system and Fcy-receptor interaction via Aab are central to EBA pathogenesis as identified in preclinical mouse models. Despite well understood post-Aab-binding effector mechanisms the clonality and etiology of Aab in EBA remains poorly understood. 

This study aims to elucidate the diversity and isotype composition of the COLVII-specific Aab response. Using a mouse model of progressive EBA, where immunization with recombinant murine COLVII induces Aab formation and disease development, the research combines phage display, next-generation sequencing, and RNA-repertoire analysis to:

1. Identify and track mCOLVII-specific Aab clonotypes

2. Characterize the natural isotypes and phylogeny of these clonotypes 

3. Express and evaluate selected Aab clones for their in vitro ability to bind mCOLVII, induce complement deposition, and assess pathogenicity in vivo.