Autoimmunity against desmocollins in pemphigus
IgG autoantibody responses against major non-desmoglein (Dsg) components of desmosomes, the desmocollins(Dsc), have been identified in patients with pemphigus herpetiformis, pemphigus vegetans, IgA pemphigus, as well as atypical and paraneoplastic pemphigus. While the pathogenic potential of autoantibodies specific for Dsg1 and Dsg3 has been extensively characterized, the pathogenicity of Dsc-specific IgG autoantibodies has only been demonstrated in vitro. Therefore, the work of the present workpackage is aimed at dissecting the mechanisms that regulate pathogenic Dsc-specific autoantibodies and the subsequent events that eventually lead to epidermal loss of adhesion. For this purpose, newly developed mouse models of autoimmunity against Dsc will be used. These models combine the characteristic molecular features of anti-Dsc ab-induced acantholysis with a blistering clinical phenotype and reproduce the active autoimmune response and the blistering disease induced by the immunization with the autoantigen and/or the final effector phase of the autoimmune response to Dsc (i.e., the tissue damage induced by the passive transfer of antibodies).
Prof. Dr. Cassian Sitaru
Universitäts-Klinik für Dermatologie und Venerologie
Schmidt T, Sitaru C, Amber K, Hertl M. BP180- and BP230-specific IgG autoantibodies in pruritic disorders of the elderly: a preclinical stage of bullous pemphigoid? Br J Dermatol. 2014 Aug;171(2):212-9.
Chiriac MT, Licarete E, Sas AG, Rados AM, Lupan I, Chiriac AM, Sitaru C. Passive transfer of collagen XVII-specific antibodies induces sustained blistering disease in adult mice. Orphanet J Rare Dis. 2013 Jan 29;8(1):17.
Oswald E, Sesarman A, Franzke C-W, Wölfle U, Bruckner-Tuderman L, Jakob T, Sitaru C. The Flavonoid Luteolin Inhibits Fc?-Dependent Respiratory Burst in Granulocytes, but Not Skin Blistering in a New Model of Pemphigoid in Adult Mice. PLoS ONE. 2012 Feb 6;7(2):e31066.
Sitaru C, Chiriac MT, Mihai S, Büning J, Gebert A, Ishiko A, et al. Induction of Complement-Fixing Autoantibodies against Type VII Collagen Results in Subepidermal Blistering in Mice. J Immunol. 2006 Sep 1;177(5):3461–8.
Sitaru C, Mihai S, Otto C, Chiriac MT, Hausser I, Dotterweich B, et al. Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen. J Clin Invest. 2005 Apr 1;115(4):870–8.