Contribution of taurine, hypoxanthine, vitamin B5 and B6 in the pathomechanism of pemphigus vulgaris

Pemphigus vulgaris (PV) is an autoimmune skin blistering disease that is clinically characterized by mucocutaneous blistering and erosions, with a severe course and it is potentially a life-threatening disease. In the vast majority of cases, PV is caused by autoantibodies targeting desmoglein 3 and 1, developed in a T-cell dependent fashion. The study of the metabolomics and lipidomics in PV showed unique signatures when compared to healthy controls. Furthermore, there are distinct metabolite profiles in PV before and after immunosuppressive treatment, and those profiles after the therapy cluster closely to those of healthy controls. For example, the plasma concentration of pantothenic acid (vitamin B5) and pyridoxine (vitamin B6) in active PV are reduced, while after the treatment, the plasma levels increase to the level of healthy donors. In contrast, taurine and hypoxanthine concentrations in active PV are increased and they return to those observed in healthy controls. It is well known, that these four altered metabolite profiles are associated with inflammatory bowel disease and arthritis, and they play a role in wound healing in cell culture models. 

We will investigate the impact of taurine, hypoxanthine, vitamins B5 and B6 on (i) T cell activation, (ii) B cell activation, and (iii) we will determine if they modulate PV-IgG-induced pathogenic changes in keratinocytes and in a human skin organ culture model of pemphigus.