Project Details
Projekt
Epitope spreading in Pemphigus
Applicants
Professor Luca Borradori, Ph.D.; Dr. Ansgar Schmidt
Subject Area
Dermatology
Immunology
Immunology
Term
from 2016 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 289113135
Epitope spreading has been linked to the chronic course and severity of distinct autoimmune disorders. Paraneoplastic pemphigus (PNP), a tumor-associated clinical variant of pemphigus is characterized by a mostly lethal outcome and a broad range of auto-antigens targeted by IgG auto-antibodies. The experiments include the generation of human monoclonal antibodies derived by immortalization of memory B-cells from PNP-patients. Subsequently, it is planned to analyse the repertoire of these immortalized memory B cells against several target antigens specific to PNP, i.e. alpha 2 macroglobulin-like 1 (A2ML1), a protease inhibitor of unknown function, the intracellular desmosomal adhesion molecules, desmoplakin, envoplakin, and periplakin, as well as plakophilin 3 (PKP3), an armadillo protein predominately expressed in skin. Specifically, we want to elucidate the relevance of the autoantigens A2ML1 and PKP3 for the loss of cellular adhesion in epithelia during the pemphigus disease as well as the molecular mechanisms that are associated with these proteins in the pathogenesis of pemphigus. Based on our findings, we expect crucial insights into epitope spreading in pemphigus and the functional relevance of auto-antigens which do not possess adhesive function, such as A2ML1.
DFG Programme
Research Units
International Connection
Switzerland
Partner Organisation
Schweizerischer Nationalfonds (SNF)
Co-Investigator
Dr. Bertrand Favre
