Desmoglein 1 and Desmoglein 3 Are the Target Autoantigens in Herpetiform Pemphigus

OBJECTIVE: To determine the cell surface autoimmune target of herpetiform pemphigus (HP). DESIGN: Serum samples of HP were examined by immunoblot studies with human epidermal extracts, enzyme-linked immunosorbent assay with baculovirus-expressed recombinant desmoglein (rDsg) 1 and rDsg3, and immunoadsorption assay with rDsg. PATIENTS: Twenty serum samples were obtained from patients with HP who have typical clinical and histological features. All serum samples showed positive staining against keratinocyte cell surfaces by indirect immunofluorescence studies with healthy human skin. RESULTS: Immunoblot results showed that of 17 HP serum samples, only 5 reacted with a 160-kd band and 1 reacted with a 130-kd band. Results of enzyme-linked immunosorbent assays with rDsg1 and rDsg3 demonstrated that of 20 HP serum samples, 16 were positive against Dsg1 and 4 were positive against Dsg3. No serum samples reacted with both. Furthermore, in 19 of 20 HP serum samples, immunoreactivity against keratinocyte cell surfaces was completely removed by preincubation with rDsg1 and rDsg3 as shown by indirect immunofluorescence, excluding a possibility that these HP sera contain autoantibodies against other cell surface molecules. CONCLUSIONS: Dsg1 and Dsg3 are the major cell surface target molecules of HP, suggesting that most cases of HP are clinical variants of pemphigus foliaceus and that the rest might be variants of pemphigus vulgaris.