Induction of keratinocyte IL-8 expression and secretion by IgG autoantibodies as a novel mechanism of epidermal neutrophil recruitment in a pemphigus variant

E. A. O'Toole, L. L. Mak, J. Guitart, D. T. Woodley, T. Hashimoto, M. Amagai, L. S. Chan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

A subset of pemphigus herpetiformis, a rare pemphigus variant, is characterized histopathologically by subcorneal acantholysis and neutrophilic infiltration. The mechanism of neutrophil infiltration is unknown, but chemokines such as IL-8 may play a role. We investigated the possible role of IL-8 in two such cases. Direct and indirect immunofluorescence studies demonstrated in vivo-bound and circulating IgG epithelial cell surface- binding autoantibodies, both predominated by IgG4 subclass. ELISA and immunoblotting studies revealed that the patients' IgG autoantibodies recognized recombinant desmoglein 1 but not desmoglein 3. Preadsorption of the patients' sera with recombinant desmoglein 1 completely removed the epidermal cell surface immunostaining. Significantly, immunohistochemistry demonstrated intense expression of IL-8, co-localized with in vivo-bound IgG, in the upper epidermis, where the acantholysis took place. Affinity-purified sera IgG from these two patients, a normal individual, and a pemphigus vulgaris patient containing desmoglein 1 autoantibodies, were incubated with normal human keratinocytes in vitro. Cells treated with these patients' IgG secreted a seven-to-nine-fold increase of IL-8 (30-37 pg/ml) compared with the controls (2-4 pg/ml) and expressed a higher intensity of cytoplasmic IL-8 staining. These data demonstrate a novel functional role for IL-8 in the pathogenesis of the neutrophil-dominant subset of pemphigus herpetiformis. The autoantibody-induced epidermal cell IL-8 expression may represent a novel mechanism of epidermal neutrophil recruitment.

Original languageEnglish (US)
Pages (from-to)217-224
Number of pages8
JournalClinical and Experimental Immunology
Volume119
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Autoimmunity
  • Chemokine
  • Immunohistochemistry
  • Neutrophils
  • Skin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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