Clearance rates of circulating and tissue-bound autoantibodies to type VII collagen in experimental epidermolysis bullosa acquisita

P>Background Epidermolysis bullosa acquisita (EBA) is a severe autoimmune skin disease characterized by autoantibodies to type VII collagen, the major component of anchoring fibrils. In this and other autoimmune bullous dermatoses, specific autoantibody detection systems are not only of diagnostic use but also allow monitoring of circulating and skin-bound autoantibodies during the course of the disease. However, little is known about their natural clearance rates in these different compartments. Objectives To study clearance rates of circulating and tissue-bound autoantibodies to type VII collagen in experimental EBA. Methods Using offspring from mice with experimentally induced EBA, we examined retention times of diaplacentally transmitted autoantibodies to type VII collagen in serum of neonatal mice by enzyme-linked immunosorbent assay and of immunoreactant deposits in skin by direct immunofluorescence microscopy. Additionally, the pathogenic potential of transmitted autoantibodies was evaluated in descendant mice. Results Immediately after birth, comparable levels of pathogenic antibody concentrations were observed in maternal and neonatal mice. The clearance time of skin-bound autoantibodies was twice as long as that of circulating autoantibodies (8 and 4 weeks, respectively). Maternofetal transfer of pathogenic autoantibodies produced specific immunopathological (IgG, IgG1, IgG2a/b and complement C3 deposits) but not histological or clinical alterations in skin of offspring mice. Conclusions Although still to be confirmed in humans, our findings add to the knowledge on turnover rates of circulating and skin-bound autoantibodies in autoimmune bullous dermatoses, which in turn may facilitate a more specific monitoring of these antibodies during the disease course, reduce the need for repeated skin biopsies, and may also be helpful in guiding treatment decisions.