Identification of desmoglein 1 as autoantigen in a patient with intraepidermal neutrophilic IgA dermatosis type of IgA pemphigus

In a 51-year-old female patient with intraepidermal neutrophilic IgA dermat osis (IEN) type of IgA pemphigus, circulating IgA, but not IgG, autoantibod ies were detected to bind to the cell surface of the whole epidermis, being much stronger in the upper epidermis. In the patient's skin a heavy intrae pidermal IgA staining was observed throughout the whole epidermis, accompan ied by a weak IgG and a more prominent C3 staining. IgA from the patient's serum showed no reactivity either with epidermal proteins by immunoblot ana lysis, or with COS 7 cells transiently transfected with mammalian cell expr ession constructs containing full length human Dsc1, Dsc2 and Dsc3. Our pat ient's IgA specifically reacted with conformational epitopes of human desmo glein (Dsg) 1 but not Dsg 3, when studied in a previously established, here for IgA antibody detection modified enzyme-linked immunoabsorbent assay (E LISA) of baculovirus expression system. The immunoreactivity against kerati nocyte cell surface was completely removed from the serum of the patient by pre-incubation with recombinant Dsg1 baculoprotein. This finding indicates that the sera possess only IgA antibodies against the extracellular domain of Dsg1 baculoprotein, but no antibodies against components of keratinocyt e cell surface other than Dsg1. This is the first case of IgA pemphigus whe re Dsg1 has been identified as the autoantigen.