Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes, characterized by the appearance of flaccid blisters and erosions that usually arise on normal-appearing skin and mucosa. PV is caused by antibodies directed against desmoglein 3 (Dsg3), an epidermal glycoprotein of the cadherin family. In animal studies, anti-Dsg3 antibodies have been shown to induce loss of cell adhesion, suggesting that Dsg3 plays an important role in disease pathogenesis. Traditionally, pemphigus antibodies are detected by direct or indirect immunofluorescence (IIF) testing, but this method tends to be subjective and often fails to distinguish PV from other bullous diseases. However, recent success in cloning the Dsg3 gene has led to the development of a specific, sensitive, enzyme-linked immunosorbent assay (ELISA) that detects PV autoantibodies. Lenz and associates compared ELISA values with autoantibody titers obtained by classic IIF in patients with PV and other dermatologic conditions to determine the specificity and sensitivity of ELISA in diagnosing PV.
Serum samples obtained from 11 patients with confirmed PV were tested for anti-Dsg3 reactivity. Forty-five patients with other bullous or nonbullous conditions were also included in the study to evaluate the specificity of ELISA and to determine whether ELISA was prone to false-positive results. In addition, 10 healthy persons were included in the analysis to serve as the control group. The Dsg3 protein used in this study was produced in the authors' laboratory.
Of the 52 PV serum samples evaluated in the study, 47 were positive by Dsg3-ELISA, for a sensitivity of 93 percent. The sensitivity increased to 98 percent when IIF-negative PV samples were excluded, suggesting that both tests have similar sensitivity. Results of ELISA were negative in 51 of the 55 non-PV serum samples. Only four of these samples were positive by ELISA, resulting in a specificity of 93 percent. These results suggest a positive correlation between Dsg3-ELISA and IIF titer. ELISA values paralleled IIF titers and, more importantly, results of both tests increased at the time of disease relapse and decreased after treatment-induced remission. ELISA values increased earlier and were more pronounced when compared with IIF titers, possibly reflecting a higher sensitivity of ELISA in detecting anti-Dsg3 antibodies.
The authors conclude that Dsg3-ELISA is a highly sensitive and specific test for detecting pathogenic Dsg3 antibodies and should be considered an additional diagnostic tool in the routine evaluation and monitoring of patients with PV.