Pathogenic IgG4 autoantibodies from endemic pemphigus foliaceus recognize a desmoglein-1 conformational epitope.

ABSTRACT: Fogo Selvagem (FS), the endemic form of pemphigus foliaceus, is mediated by pathogenic IgG4 autoantibodies against the amino-terminal extracellular cadherin domain of the desmosomal cadherin desmoglein 1 (Dsg1). Here we define the detailed epitopes of these pathogenic antibodies. Proteolytic footprinting showed that IgG4 from 95% of FS donor sera (19/20) recognized a 16-residue peptide (A¹²⁹LNSMGQDLERPLELR¹⁴⁴) from the EC1 domain of Dsg1 that overlaps the binding site for an adhesive-partner desmosomal cadherin molecule. Mutation of Dsg1 residues M¹³³ and Q¹³⁵ reduced the binding of FS IgG4 autoantibodies to Dsg1 by ∼50%. Molecular modeling identified two nearby EC1 domain residues (Q⁸² and V⁸³) likely to contribute to the e

SUBMITTER: Evangelista F 

PROVIDER: S-EPMC5902409 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature