title: Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2-based swapped molecules.
abstract: Epitope spreading is involved in inducing and maintaining self-reactivity. Epitope spreading in pemphigus vulgaris (PV), caused by IgG autoantibodies to desmoglein 3 (Dsg3) and Dsg1, was previously analyzed using Dsg3/Dsg1 extracellular domain-swapped molecules. However, precise identification of the responsible epitopes in each molecule by using only this method was problematic. In this study, we studied epitope spreading in PV by a novel immunoprecipitation-immunoblot method using Dsg3 (or Dsg1)/Dsg2 domain-swapped molecules, which overcomes the problems associated with the previous approaches. We analyzed the antigenic epitopes recognized by 212 sera collected from 53 PV patients at multiple disease stages. The major epitopes were present at the N-terminal region of Dsgs and were unchanged over the course of the disease in both anti-Dsg3 mucosal dominant-type PV and anti-Dsg3/Dsg1 mucocutaneous-type PV. These N-terminal epitopes were calcium dependent. Circulating antibodies in paraneoplastic pemphigus and pemphigus herpetiformis had unique epitope distributions, although the Dsg N-termini still contained the major epitopes. These results suggest that, after onset, intramolecular and intermolecular epitope spreading among extracellular domains on Dsg3 and Dsg1 is rare in PV and has no correlation with disease course.
authors.affiliation: Department of Dermatology, Kurume University School of Medicine and Kurume University Institute of Cutaneous Cell Biology, Fukuoka, Japan.
authors.forename: Bungo
authors.initials: B
authors.lastname: Ohyama
authors.forename: Koji
authors.initials: K
authors.lastname: Nishifuji
authors.forename: Po Tak
authors.initials: PT
authors.lastname: Chan
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Takuto
authors.initials: T
authors.lastname: Yamashita
authors.forename: Norito
authors.initials: N
authors.lastname: Ishii
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hamada
authors.forename: Teruki
authors.initials: T
authors.lastname: Dainichi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koga
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsuruta
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D051183:Desmoglein 1 / Q000276:immunology; D051301:Desmoglein 2 / Q000276:immunology*; D051184:Desmoglein 3 / Q000276:immunology; D018450:Disease Progression; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000097:blood*; D047468:Immunoprecipitation; D008137:Longitudinal Studies; D010257:Paraneoplastic Syndromes / Q000097:blood / Q000276:immunology; D010392:Pemphigus / Q000097:blood / Q000276:immunology*; D017434:Protein Structure, Tertiary; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D051183:Desmoglein 1; D051301:Desmoglein 2; D051184:Desmoglein 3; D000939:Epitopes; D007074:Immunoglobulin G