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Subproject 1

Human leukocyte antigen (HLA)-transgenic mice as a pre-clinical model of pemphigus vulgaris



Pemphigus vulgaris (PV) serves as a model disease for an organ-specific, autoantibody-mediated autoimmune disorder. In PV there is a strong genetic association with distinct human leukocyte antigen (HLA) class II alleles. A major aim of this project is to analyse the immune mechanisms that are essential for the development of the disease in an HLA-class II-transgenic mouse model of PV. The role of autoreactive CD4+ T-lymphocytes, that are activated by recognizing defined areas of the major autoantigen demoglein 3(Dsg3), and their function of providing help for the production of Dsg3-specific autoantibodies, that are essential in the pathogenesis of PV, will be investigated and characterized in these mice. Different subtypes of Dsg3-reactive CD4+ T-lymphocytes will be analysed phenotypically and on a functional level. Based on their functional characteristics specific CD4+ T-lymphocyte subtypes will be targeted by applying DNAzyme. A key objective of the project is the induction of a Dsg3-specific T-cell tolerance in this mouse model. The immune mechanisms leading to tolerance induction will be characterized including the identification of regulatory immune cells (regulatory T and B cells) as well as of soluble factors (cytokines). The principal understanding in this pre-clinical model will provide an important basis for the phase Ib trial that investigates the Dsg3-specific tolerance induction in PV patients and the results will lead to an improved understanding of the pathogenesis of this autoimmune disorder.


Prof. Dr. Rüdiger Eming
Universitätsklinikum Gießen und Marburg GmbH
Standort Marburg
Klinik für Dermatologie und Allergologie

Prof. Dr. Holger Garn
Philipps-Universität Marburg
Fachbereich Medizin
Institut für Laboratoriumsmedizin und Pathobiochemie, Molekulare Diagnostik