Demonstration of an Adhering-Junction Molecule (Plakoglobin) in the Autoantigens of Pemphigus Foliaceus and Pemphigus Vulgaris

• Published in: The New England journal of medicine Vol. 321; no. 10; pp. 631 - 635
• Main Authors: Korman, Neil J, Eyre, Russell W, Klaus-Kovtun, Vera, Stanley, John R
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 07.09.1989
• Subjects: Autoantibodies - analysis; Autoantigens; Autoantigens - analysis; Autoimmune diseases; Binding Sites; Biological and medical sciences; Bullous diseases of the skin; Catenin; Cell surface; Chemical bonds; Chloride; Cytoskeletal Proteins - immunology; Cytoskeletal Proteins - isolation & purification; Dermatology; Desmogleins; Desmoplakins; Desmosomes - analysis; Desmosomes - immunology; Epidermis - immunology; Esophagus; gamma Catenin; Humans; Immunoglobulins; Keratinocytes; Medical sciences; Monoclonal antibodies; Pemphigus; Pemphigus - immunology; Pemphigus - metabolism; Peptides - immunology; Polypeptides; Proteins; Skin diseases; Sodium; Antigen; Bullous dermatosis; Human; Binding; Proteins; Skin disease; Autoantigen; Immunological investigation; Pemphigus foliaceous; Epithelial cell; Pemphigus vulgaris
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198909073211002

Pemphigus foliaceus and pemphigus vulgaris are skin diseases in which antibodies against the cell surface of keratinocytes destroy the adhesion between epidermal cells, producing blisters. Patients with pemphigus foliaceus have antibodies to a complex of three polypeptides of 260, 160, and 85 kd (the foliaceus complex), whereas patients with pemphigus vulgaris have antibodies to a complex of 210-kd, 130-kd, and 85-kd polypeptides (the vulgaris complex). The 160-kd polypeptide of the foliaceus complex has been identified as desmoglein, a desmosomal glycoprotein. We suspected that the 85-kd component in both these antigenic complexes might be plakoglobin, another molecule in the adhering junctions of cells. To characterize these antigenic complexes, we used the serum of five patients with pemphigus foliaceus, that of four patients with pemphigus vulgaris, and monoclonal antiplakoglobin antibodies. We found that monoclonal antibodies to plakoglobin immunoprecipitated the 85-kd polypeptide from the dissociated foliaceus and vulgaris complexes and precipitated both complexes from epidermal extracts. Serum from patients with pemphigus foliaceus or pemphigus vulgaris (but not from four normal controls) bound desmoglein and the 130-kd polypeptide, respectively, showing that these peptides (and not plakoglobin) are the antigenic binding sites in these disorders. We conclude that plakoglobin, a protein of the adhering junctions of epidermal cells, is the 85-kd molecule in the antigenic complexes found in both pemphigus foliaceus and pemphigus vulgaris, although it is not the binding site in either disorder. (N Engl J Med 1989; 321:631–5.) PEMPHIGUS is an intraepidermal blistering disease in which there is a loss of adhesion between cells, a process called acantholysis, as a consequence of autoantibodies' binding to the cell surface. 1 It occurs in two distinct forms. In pemphigus foliaceus, skin blisters develop high in the epidermis, whereas in pemphigus vulgaris, skin and mucosal blisters develop lower in the epidermis, just above the basal keratinocytes. The earliest ultrastructural changes in pemphigus foliaceus may involve alterations in the desmosome–tonofilament complex, whereas in pemphigus vulgaris the earliest change is the loss of cell–cell contact between desmosomes, which are sites of attachment between epithelial . . .