Antibodies against keratinocyte antigens other than desmogleins 1 and 3 can induce pemphigus vulgaris-like lesions

Pemphigus is an autoimmune disease of skin adhesion associated with autoant ibodies against a number of keratinocyte antigens, such as the adhesion mol ecules desmoglein (Dsg) 1. and 3 and acetylcholine receptors. The notion th at anti-Dsg antibodies alone are responsible for blisters in patients with permphigus vulgaris (PV) stems from the ability of rDsg1 and rDsg3 to absor b antibodies that cause PV-like skin blisters in neonatal mice. Here, we de monstrate that PV IgGs fluted from rDsg1-Ig-His and rDsg3-Ig-His show simil ar antigenic profiles, including the 38-, 43-, 115-, and 190-kDa keratinocy te proteins and a non-Dsg 3 130-kDa polypeptide present in keratinocytes fr om Dsg 3 knockout mouse. We injected into Dsg 3-lacking mice the PV IgGs th at did not cross-react with the 160-kDa Dsg 1 or its 45-kDa immunoreactive fragment and that showed no reactivity with recombinant Dsg I. We used bo t h the Dsg3(null) mice with a targeted mutation of the Dsg3 gene and the "ba lding" Dsg3(bal)/Dsg3(bal) mice that carry a spontaneous null mutation in D sg3. These PV IgGs caused gross skin blisters with PV-like suprabasal acant holysis and stained perilesional epidermis in a Fishnet-like pattern, indic ating that the PV phenotype can be induced without anti-Dsg 3 antibody. The anti-Dsg 1 antibody also was not required, as its presence in PV IgG does not alter the PV-like phenotype in skin organ cultures and because pemphigu s foil aceus IgGs produce a distinct phenotype in Dsg3(null) mice. Therefor e, mucocutaneous lesions in PV patients could be caused by non-Dsg antibodi es.