Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus

Objective: To determine the cell surface autoimmune target of herpetiform p emphigus (HP). Design: Serum samples of HP were examined by immunoblot studies with human epidermal extracts, enzyme-linked immunosorbent assay with baculovirus-expr essed 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 posit ive staining against keratinocyte cell surfaces by indirect immunofluoresce nce studies with healthy human skin. Results: Immunoblot results showed tha t of 17 HP serum samples, only 5 reacted with a 160-kd band and 1 reacted w ith a 130-kd band. Results of enzyme-linked immunosorbent assays with rDsg1 and rDsg3 demonstr ated 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 surfa ces was completely removed by preincubation with rDsg 1 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 H P, suggesting that most cases of HP are clinical variants of pemphigus foli aceus and that the rest might be variants of pemphigus vulgaris.