TY - JOUR
T1 - Pathogenicity and Epitope Characteristics of Anti-Desmoglein-1 from Pemphigus Foliaceus Patients Expressing only IgG1 Autoantibodies
AU - Hacker-Foegen, Mary K.
AU - Janson, Marleen
AU - Amagai, Masayuki
AU - Fairley, Janet A.
AU - Lin, Mong Shang
N1 - Funding Information:
The authors thank Dr Zhi Liu at the Department of Dermatology, University of North Carolina at Chapel Hill, for his design and construction of Dsg1–GST fusion proteins and Dr Zelmira Lazarova for her invaluable suggestions. This study was supported in part by U.S. Public Health Service Grants RO1-AI48348 (M.S.L.) from the National Institutes of Health and by a Merit Award from the Veterans Administration Central Office (J.A.F).
PY - 2003/12
Y1 - 2003/12
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1523-1747.2003.12608.x
DO - 10.1111/j.1523-1747.2003.12608.x
M3 - Article
C2 - 14675185
AN - SCOPUS:0347624708
SN - 0022-202X
VL - 121
SP - 1373
EP - 1378
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 6
ER -
