TP B1: Pemphigus vulgaris: Expression profiling in patients and development of a novel animal model

Pemphigus vulgaris is an IgG-mediated autoimmune disease of stratified squamous epithelia, such as the skin and oral mucosa. IgG autoantibodies are raised against cell-cell adhesion molecules found in desmosomes. This leads to a loss of cellular adhesion, resulting in blistering and erosion formation. The characteristic autoantibodies are Desmoglein 1 and Desmoglein 3.

The pathophysiological role of B cells has been characterized in mouse models of pemphigus and in patients, revealing important insights into the underlying mechanisms of autoimmunity.

This project  focusses on analyzing the longitudinal B cell transcriptome of patients suffering from pemphigus vulgaris. In addition we aim to measure the number of desmoglein 3–specific circulating B-cells. We will obtain blood samples at different time points before, during and after treatment.

For the transcriptome analysis we will perform next generation RNA sequencing, which allows the detection of the whole expressed genes. The separation of B and T cells is followed by RNA-isolation. Afterwards the RNA sequencing is performed.

Furthermore we want to establish a new active mouse model for the disease. Moreover the project aims to determine the key regulatory signaling pathways and expression patterns in B cells in pemphigus and clarify their prognostic value.