ORIGINAL ARTICLE Neonatal Fc receptor deficiency protects from tissue injury in experimental epidermolysis bullosa acquisita Alina Sesarman & Ana Gabriela Sitaru & Florina Olaru & Detlef Zillikens & Cassian Sitaru Received: 9 January 2008 / Revised: 11 April 2008 / Accepted: 25 April 2008 / Published online: 10 June 2008 # Springer-Verlag 2008 Abstract Epidermolysis bullosa acquisita (EBA) is an auto- immune blistering disease caused by autoantibodies against type VII collagen. The neonatal Fc receptor (FcRn) regulates immunoglobulin G (IgG) homeostasis and thus controls serum levels of antibodies. In this study, we investigated the effects of FcRn deficiency on the levels of autoantibodies against type VII collagen and blistering in EBA. For this purpose, rabbit IgG against murine type VII collagen was injected into FcRn- deficient and wild-type (n =10 per group) mice. Enzyme- linked immunosorbent assay levels of serum IgG against type VII collagen were significantly lower in mutant compared with wild-type mice. Analysis of serum levels of specific autoantibodies induced in FcRn-deficient and wild-type mice (n =10 per group) by immunization with type VII collagen showed significantly lower serum levels of IgG against type VII collagen in FcRn-deficient mice compared with wild-type animals. Importantly, the extent of blistering disease after injection of IgG against type VII collagen was significantly reduced in FcRn-deficient mice compared to wild-type controls. Our data demonstrate that FcRn maintains levels of pathogenic autoantibodies and thereby promotes tissue injury in experimental EBA. Therefore, modulation of FcRn function using inhibitors may reduce pathogenic IgG levels, offering therapeutic benefit in patients with antibody-mediated diseases. Keywords Autoantibodies . Epidermolysis bullosa acquisita . Extracellular matrix . Inflammation Abbreviations EBA epidermolysis bullosa acquisita IF immunofluorescence J Mol Med (2008) 86:951–959 DOI 10.1007/s00109-008-0366-7 DO00366; No of Pages Electronic supplementary material The online version of this article (doi:10.1007/s00109-008-0366-7) contains supplementary material, which is available to authorized users. A. Sesarman : F. Olaru : D. Zillikens : C. Sitaru Department of Dermatology, University of Lübeck, Lübeck, Germany A. G. Sitaru Institute for Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany C. Sitaru (*) Department of Dermatology, University of Freiburg, Hauptstrasse 7, 79104 Freiburg, Germany e-mail: csitaru@fastmail.fm ALINA SESARMAN is currently a Ph.D. student at the Department of Experimental Biology, Bolyai University, Cluj-Napoca, Romania. During her stay in the laboratory of Dr. Cassian Sitaru, she focused on the mechanisms of generation and catabolism of pathogenic autoantibodies using experimental animal models of the organ-specific autoimmune disease epidermolysis bullosa acquisita. CASSIAN SITARU received his MD from the Julius-Maximilians University of Würzburg, Germany. Presently, he is a junior group leader at the Department of Dermatology, University of Freiburg, Germany. His research activity focuses on the molecular pathogenesis of autoimmune diseases using ex vivo and animal models of autoantibody- induced blistering of skin and mucous membranes.