The Distribution of IgA Pemphigus Antigen in Human Skin and the Role of IgA Anti-Cell Surface Antibodies in the Induction of Intraepidermal Acantholysis

Abstract

IgA pemphigus is an uncommon intraepidermal vesiculopustular disease that has clinical and histologic similarity to subcorneal pustular dermatosis and pemphigus foliaceus. All patients have IgA antibodies bound to the epidermal cell surface, and half of the patients have circulating IgA anti-cell surface antibodies detected by standard immunofluorescence testing. We studied the distribution of IgA pemphigus antigen in human skin and the pathogenetic role of circulating IgA antibodies in the induction of intraepidermal vesicle formation. We used skin specimens from numerous sites of two cadavers, as well as from neonatal foreskin, and serum specimens of two patients with IgA pemphigus. Organ culture and immunofluorescence studies revealed the following: (1) IgA pemphigus antibodies bound preferentially to the granular layer in the vast majority of skin sites that were tested. In one cadaver, binding was preferential to the spinous layer of plantar and buttock skin. No binding was observed in oral and esophageal mucosa. (2) Neither bound nor circulating IgA antibody was complement fixing. (3) One IgA pemphigus serum specimen that was negative by standard immunofluorescence had IgA antibodies that bound the epidermal cell surface after incubation under explant culture conditions. (4) Both IgA pemphigus serum specimens induced acantholysis in skin explant cultures. When antibodies from one IgA pemphigus serum specimen are used, the expression of IgA pemphigus antigen in human skin shows regional variability, interindividual variability, and variability in the microscopic distribution within the epidermal cell layers. IgA pemphigus antibodies play a role in the pathogenesis of IgA pemphigus. The skin explant culture is more sensitive than is standard immunofluorescence to detect circulating IgA antibodies.