Identification of pemphigus vulgaris antigen extracted from normal human epidermis and comparison with pemphigus foliaceus antigen.

Abstract

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.

Pemphigus vulgaris antigen, a desmoglein type of cadherin, is localized within keratinocyte desmosomes

“…Each serum immunoprecipitated the characteristic PVA complex (containing the 130-kD antigen) from extracts of normal epidermis or cultured keratinocytes (9,33). This immunoprecipitation has been shown to be specific for PV patient sera (9,33).…”

Desmosome assembly, homeostasis, and desmosomal disease

“…128 These bullae rupture and heal, leaving a yellow-brown crust and a nontender lesion. 129 Fluid obtained from these bullae is found to contain S. aureus. This is the mildest form of the staphylococcal exfoliating disease as the surrounding skin remains normal, and there are no systemic symptoms or signs.…”

Absorption of pathogenic autoantibodies by the extracellular domain of pemphigus vulgaris antigen (Dsg3) produced by baculovirus.

“…A target molecule of these pathogenic autoantibodies, PV antigen (PVA), has been characterized as a 130-kD glycoprotein by immunoprecipitation and immunoblot analyses (7)(8)(9)(10). Recently, cDNA for PVA has been isolated by immunoscreening a human keratinocyte expression cDNA library with affinity-purified PV IgG (11).…”