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

A subset of pemphigus herpetiformis, a rare pemphigus variant, is character ized histopathologically by subcorneal acantholysis and neutrophilic infilt ration. 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 demonstrate d in vivo-bound and circulating IgG epithelial cell surface-binding autoant ibodies, both predominated by IgG4 subclass. ELISA and immunoblotting studi es revealed that the patients' IgG autoantibodies recognized recombinant de smoglein 1 but not desmoglein 3. Preadsorption of the patients' sera with r ecombinant desmoglein 1 completely removed the epidermal cell surface immun ostaining. Significantly, immunohistochemistry demonstrated intense express ion of IL-8, co-localized with in vivo-bound IgG, in the upper epidermis, w here 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 keratinocyte s 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 neu trophil-dominant subset of pemphigus herpetiformis. The autoantibody-induce d epidermal cell IL-8 expression may represent a novel mechanism of epiderm al neutrophil recruitment.