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.

Immunoprecipitations of cultured keratinocyte extracts have shown that pemphigus vulgaris (PV) sera bind a polypeptide of 210,000 mol wt with disulfide-linked chains of 130,000 and 85,000 mol wt. To identify proteins in normal human skin recognized by PV antibodies, we performed immunoprecipitations of normal human epidermal extracts. All 22 PV sera tested immunoprecipitated a complex of polypeptides (PV complex) of 210,000, 130,000, and 85,000 mol wt, after reduction. One-and two-dimensional gel electrophoresis showed that the 130,000-and 85,000-mol-wt polypeptides of the PV antigen from both cultured keratinocytes and epidermis have identical charges and sizes. In addition to precipitating the PV complex, 14 of 22 PV sera also have antibodies to a calciumsensitive epitope on a different complex of polypeptides (PF complex) which has previously been shown to be precipitated by all pemphigus foliaceus (PF) sera. The PF complex consists of polypeptides of 260,000, 160,000, 110,000, and 85,000 mol wt. Although the majority of PV sera also precipitate the PF complex, no PF sera precipitate the PV complex. Thus, PV and PF can be absolutely distinguished on a molecular level using the patients' autoantibodies. The PV and PF complexes, although distinct, have certain similarities. The 85,000-mol-wt polypeptide of each is identical. The 160,000-mol wt-peptide of the PF complex and the 130,000-mol-wt peptide of the PV complex have the same isoelectric point and both are capable of disulfide linkage to the 85,000-mol-wt polypeptide. The PV and PF complexes are closely related and may prove important in cell adhesion.

We studied the response to a standard skin injury in the involved and uninvolved skin of twenty-four subjects with psoriasis to determine whether a relationship exists between disease activity and the Koebner reaction. We found that 25% of patients had a positive Koebner reaction and 67% had a positive 'reverse' Koebner reaction (psoriasis clearing following skin injury). If psoriasis occurred in one area of injury, all injured areas developed psoriasis, and 'all-or-none' phenomenon. If psoriasis cleared from the traumatized area, no psoriasis occurred in the uninvolved sites. The 'reverse' Koebner reaction and the Koebner reaction are thus mutually exclusive. Disease activity, by our criteria, did not predict a positive Koebner reaction, but a positive Koebner reaction did predict subsequent disease activity. These observations suggest that humoral factors govern the development of clearing or psoriasis after a standard injury.

Pemphigus foliaceus (PF) patients have antibodies against a tightly, but noncovalently bound complex of polypeptides, which consists of desmoglein I (DGI) and other, possibly desmosomal, proteins. Most PF antibodies bind a calcium-sensitive epitope on this complex and chelation of calcium destroys the reactivity of these sera with the complex, but not the complex itself. The PF sera that do bind the desmosomal complex in the absence of calcium are those sera capable of binding denatured DGI on immunoblotting, and these same sera also immunoprecipitate only DGI when the desmosomal complex is dissociated with SDS. These findings demonstrate that autoantibodies against a complex of desmosome-associated proteins are characteristic of PF and define a calcium-sensitive conformational epitope on this complex.