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

doi:10.1111/j.1523-1747.2003.12608.x

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Pathogenicity and epitope characteristics of anti-desmoglein-1 from pemphigus foliaceus patients expressing only IgG1 autoantibodies

Journal article

Open access

Peer reviewed

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 and Mong-Shang Lin

Journal of investigative dermatology, Vol.121(6), pp.1373-1378

12/2003

DOI: 10.1111/j.1523-1747.2003.12608.x

PMID: 14675185

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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 autoanti-bodies 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 auto-antibodies 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.

Protein Structure, Tertiary

Humans

Pemphigus - etiology

Epitopes - immunology

Autoantibodies - immunology

Animals

Cadherins - immunology

Immunoglobulin G - immunology

Cadherins - chemistry

Desmoglein 1

Pemphigus - immunology

Protein Conformation

Epitopes - chemistry

Mice

Mice, Inbred BALB C

Details

Title: Subtitle: Pathogenicity and epitope characteristics of anti-desmoglein-1 from pemphigus foliaceus patients expressing only IgG1 autoantibodies
Creators: Mary K Hacker-Foegen - Department of Dermatology, Medical College of Wisconsin, Milwaukee 53226, USA
Marleen Janson
Masayuki Amagai
Janet A Fairley
Mong-Shang Lin
Resource Type: Journal article
Publication Details: Journal of investigative dermatology, Vol.121(6), pp.1373-1378
Publisher: United States
DOI: 10.1111/j.1523-1747.2003.12608.x
PMID: 14675185
ISSN: 0022-202X
eISSN: 1523-1747
Grant note: R01-AI48348 / NIAID NIH HHS
Language: English
Date published: 12/2003
Academic Unit: Dermatology
Record Identifier: 9984025324802771

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