Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2-based swapped molecules

Bungo Ohyama, Koji Nishifuji, Po Tak Chan, Atsushi Kawaguchi, Takuto Yamashita, Norito Ishii, Takahiro Hamada, Teruki Dainichi, Hiroshi Koga, Daisuke Tsuruta, Masayuki Amagai, Takashi Hashimoto

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49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1158-1168
Number of pages11
JournalJournal of Investigative Dermatology
Volume132
Issue number4
DOIs
Publication statusPublished - 2012 Apr

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Ohyama, B., Nishifuji, K., Chan, P. T., Kawaguchi, A., Yamashita, T., Ishii, N., Hamada, T., Dainichi, T., Koga, H., Tsuruta, D., Amagai, M., & Hashimoto, T. (2012). Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2-based swapped molecules. Journal of Investigative Dermatology, 132(4), 1158-1168. https://doi.org/10.1038/jid.2011.448