AUTHOR=Papara Cristian , Karsten Christian M. , Ujiie Hideyuki , Schmidt Enno , Schmidt-Jiménez Leon F. , Baican Adrian , Freire Patricia C. , Izumi Kentaro , Bieber Katja , Peipp Matthias , Verschoor Admar , Ludwig Ralf J. , Köhl Jörg , Zillikens Detlef , Hammers Christoph M. TITLE=The relevance of complement in pemphigoid diseases: A critical appraisal JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.973702 DOI=10.3389/fimmu.2022.973702 ISSN=1664-3224 ABSTRACT=

Pemphigoid diseases are autoimmune chronic inflammatory skin diseases, which are characterized by blistering of the skin and/or mucous membranes, and circulating and tissue-bound autoantibodies. The well-established pathomechanisms comprise autoantibodies targeting various structural proteins located at the dermal-epidermal junction, leading to complement factor binding and activation. Several effector cells are thus attracted and activated, which in turn inflict characteristic tissue damage and subepidermal blistering. Moreover, the detection of linear complement deposits in the skin is a diagnostic hallmark of all pemphigoid diseases. However, recent studies showed that blistering might also occur independently of complement. This review reassesses the importance of complement in pemphigoid diseases based on current research by contrasting and contextualizing data from in vitro, murine and human studies.