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.
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.
Nuclear magnetic resonance titration of the interaction between pemphigus vulgaris autoantibodies and REWVKFAKPCRE, a therapeutic desmoglein 3 peptide
LUCCHESE, Alberta;
2016
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
