Pathogenicity and Epitope Characteristics of Anti-Desmoglein-1 from Pemphigus Foliaceus Patients Expressing only IgG1 Autoantibodies

Mary K. Hacker-Foegen, Marleen Janson, Masayuki Amagai, Janet A. Fairley, Mong Shang Lin

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Pemphigus foliaceus (PF) is an antibody-mediated autoimmune disorder with IgG1 and IgG4 as the predominant subclasses of autoantibodies against a desmosomal glycoprotein, desmoglein-1 (Dsg1). Previously, we found that the IgG4 anti-Dsg1 autoantibodies only recognize a conformational epitope(s), whereas the IgG1 autoantibodies recognize both conformational and linear epitopes but do not display pathogenicity in the passive transfer animal model. The purpose of this study was to analyze the epitopes recognized by autoantibodies from a subset of PF patients who only express anti-Dsg1 of the IgG1 isotype throughout the course of their diseases and to further characterize the pathogenicity of their IgG1 anti-Dsg1. We found that IgG1 autoantibodies in this subset of PF patients, similar to IgG4 autoantibodies from other PF patients, are able to bind both human and mouse skin and induce the experimental PF in mice. Moreover, a detailed epitope mapping reveals that the conformational epitopes recognized by IgG1 autoantibodies from these PF patients are restricted to the first 161 amino acids of Dsg1, whereas the linear epitopes are spread throughout the entire ectodomain. In conclusion, our study reveals that the isotype of IgG does not necessarily determine the epitopes and pathogenicity of pemphigus autoantibodies.

Original languageEnglish
Pages (from-to)1373-1378
Number of pages6
JournalJournal of Investigative Dermatology
Volume121
Issue number6
DOIs
Publication statusPublished - 2003 Dec

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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