Bullous pemphigoid (BP) and anti-laminin 332 mucous membrane pemphgoid (anti-LAM332 MMP) belong to the group of subepidermal blistering autoimmune skin diseases. These diseases are characterized by IgG autoantibodies against two structural proteins of the dermal-epidermal junction, type XVII collagen (Col17) in BP and laminin 332 in anti-LAM332 MMP. Autoantibody binding induces an inflammatory process which finally leads to blister formation.

The way IgG Fc-fragments are glycosylated is essential for the antibody effector function. Former studies indicated that less galactosylated, sialysated IgG antibodies have pro-inflammatory effects and higher galactosylated, sialysated IgG antibodies are associated with an anti-inflammatory effect. It was already shown that in patients with rheumatoid arthritis, the amount of IgG without terminal galactose and sialic acid is increased. Also, the elimination of the glycan chain of the IgG antibodies led to reduced pathogenicity in two models of experimental epidermolysis bullosa acquisita, another  subepidermal blistering autoimmune characterized by autoimmunity to type VII collagen.

In the present project, I want to compare the glycosylation structure of IgG antibodies of healthy blood donors (young and old) with the glycosylation structure of total and NC16A (domain of Col17)-specific IgG autoantibodies in BP patients. We will also explore the pathogenic relevance of the lack of galactose and sialic acid of Col17specific antibodies from patients and rabbits in different ex vivo and in vivo models.

In the second part of my project, I will aim at developing a novel mouse model for anti-LAM332 MMP. Data from anti-LAM332 MMP patients suggest that autoantibodies against the ?3-chain of laminin 332, an important extracellular matrix protein, are pathogenic. Now, I would like to proof this hypothesis by different ex vivo and in vivo models and further identify key pathogenic factors of this disease.