Nuclear magnetic resonance titration of the interaction between pemphigus vulgaris autoantibodies and REWVKFAKPCRE, a therapeutic desmoglein 3 peptide

Background: Pemphigus vulgaris (PV) is an autoimmune skin disease, the primary autoantigen of which is the desmosomal cadherin desmoglein (Dsg)3. The exact defin-ition of Dsg3 epitopes and their relationship(s) to the pathophysiology of blister formation are important for the advancement of efforts to develop more effective and specific therapies for PV. Aim: To characterize the binding of autoantibodies from patients with PV to a Dsg3 peptide, REWVKFAKPCRE, which shows therapeutic effectiveness but does not induce pathogenic antibodies. Methods: We carried out a titration experiment of the reaction between PV autoantibodies and the peptide Dsg349-60REWVKFAKPCRE using nuclear magnetic resonance (NMR) spectroscopy. Results: The interaction between Dsg349-60REWVKFAKPCRE and PV autoantibodies at concentrations of 20, 40 and 60 mg was found to involve R49 and A55 residues. Conclusions: Our data seem to suggest that the REWVKFAKPCRE peptide may mimic epitopic Dsg3 extracellular sequences related to pathogenic autoantibodies.