Human autoantibodies against a desmosomal core protein in pemphigus foliaceus.

Abstract

Pemphigus foliaceus (PF) is a human autoimmune disease in which antibodies are directed against the cell surface of epidermal cells with resultant blister formation. The histopathology of these blisters indicates that cells have detached from each other, and EM of early blisters shows diminished numbers, to complete loss, of desmosomes as well as abnormalities of the tonofilament-desmosome complex. Autoantibodies from certain PF patients bound to a desmosomal core glycoprotein called desmoglein (DG) I. Proteins in extracts of normal human epidermis were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE), then transferred to nitrocellulose or 2-aminophenylthioether paper for immunoperoxidase staining. Results of these immunoblots indicated that sera from 6 of 13 PF patients specifically and intensely stained an .apprx. 160,000 MW polypeptide, PF antigen. Such staining was not seen with normal human sera or sera from patients with pemphigus vulgaris or bullous pemphigoid, 2 autoimmune blistering skin diseases that are clinically, histologically and immunochemically distinct from PF. Rabbit antiserum directed against DGI, that was isolated from bovine muzzle desmosomes, stained a polypeptide band which co-migrated with PF antigen. When proteins from extracts of normal human epidermis were electrophoresed in 2 dimensions (isoelectric focusing, then SDS-PAGE) before transfer to nitrocellulose for immunoperoxidase staining, PF antibodies and antibodies to DGI stained identical spots. PF sera as well as PF IgG that was affinity purified with PF antigen from normal human epidermis, both selectively bound to DGI extracted from bovine muzzle desmosomes. The studies demonstrate that the human autoantibodies from certain patients with PF, a disease of epidermal cell adhesion, are directed against a desmosomal core protein.