The role of subclass switching in the pathogenesis of endemic pemphigus foliaceus

S. J.P. Warren, L. A. Arteaga, E. A. Rivitti, V. Aoki, G. Hans-Filho, B. F. Qaqish, M. S. Lin, G. J. Giudice, L. A. Diaz

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Endemic pemphigus foliaceus, like the sporadic form seen in the developed world, is mediated by IgG antibodies to desmoglein-1. We studied an endemic focus in Limao Verde, Brazil, where disease prevalence is 3.4%. We previously detected IgG antibodies to desmoglein-1 in 97% of patients, but also in 55% of normal subjects in the endemic focus, with progressively lower levels in normal subjects in surrounding areas. An environmental trigger is hypothesized to explain these and other findings. In this study we sought to determine if patients and enzyme-linked-immunosorbent-assay-positive normal subjects in Limao Verde differ in IgG subclass response to desmoglein-1. We developed a sensitive and specific subclass enzyme-linked immunosorbent assay using recombinant desmoglein-1 and standardized the assay to enable comparability between the four subclasses. We found that normal subjects have an IgG1 and IgG4 response, whereas patients have similar levels of IgG1 but a mean 19.3-fold higher IgG4 response. Patients in remission have a weak IgG4 response, and a 74.3-fold higher IgG4 response is associated with active disease. Finally, in five patients in whom we had blood samples from both before and after the onset of clinical disease, a mean 103.08-fold rise in IgG4 was associated with onset of clinical disease, but only a mean 3.45-fold rise in IgG1. These results suggest that the early antibody response in normal subjects living in the endemic area and in patients before the onset of clinical disease is mainly IgG1. Acquisition of an IgG4 response is a key step in the development of clinical disease.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalJournal of Investigative Dermatology
Volume120
Issue number1
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Autoantibodies
  • Autoimmunity
  • Desmoglein
  • Fogo selvagem
  • IgG4

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Warren, S. J. P., Arteaga, L. A., Rivitti, E. A., Aoki, V., Hans-Filho, G., Qaqish, B. F., Lin, M. S., Giudice, G. J., & Diaz, L. A. (2003). The role of subclass switching in the pathogenesis of endemic pemphigus foliaceus. Journal of Investigative Dermatology, 120(1), 1-5.