Monitoring of autoreactive T cells responses in active and remittent pemphigus vulgaris

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T lymphocytes are considered to be critical initiators and perpetuators of autoimmune responses which are the basis for several autoimmune disorders. The pathogenesis of pemphigus largely depends on IgG autoantibodies which are formed by B cells/plasma cells which require help from autoreactive T-lymphocytes. In the 1st funding period of PEGASUS, we have established seral ex vivo assays aimed at identifying peripheral blood T cell responses against desmoglein 3 (Dsg3), the major autoantigen of pemphigus vulgaris. In addition, we managed to detect T-cells specific for small peptide components of Dsg3 in the blood of pemphigus patients. These Dsg3 peptides are of particular interest because they can be applied under tolerogenic conditions to restore immune tolerance against Dsg3. We have encountered novel technologies including ELISPOT analysis and dextramer staining to detect Dsg3 peptide-specific T cells. We now want to refine these techniques to also monitor the presence of Dsg3 reactive T cell subsets at different stages of the disease and under different therapeutic regimens. In addition, we plan to study additional immune cells, such as Dsg3-reactive B cells which largely depend on T cell activation and pro- and anti-inflammatory factors which may contribute to the pemphigus pathogenesis, These finding will hopefully be more specific therapeutic markers in PV and may contribute to a better understanding of the involvement of distinct immune cells in the pathogenesis of pemphigus.