Pemphigus vulgaris and pemphigus foliaceus are two closely related, but cli
nically and histologically distinct, autoimmune skin diseases. The autoanti
gens for pemphigus vulgaris and pemphigus foliaceus are desmoglein 3 and de
smoglein 1, respectively. The anti-desmoglein 1 antibodies in pemphigus fol
iaceus and anti-desmoglein 3 antibodies in pemphigus vulgaris are pathogeni
c as determined by immunoglobulin G passive transfer animal models. More th
an 50% of pemphigus vulgaris sera also contain anti-desmoglein 1 autoantibo
dies; however, the pathogenicity of the anti-desmoglein 1 autoantibodies in
pemphigus vulgaris remains unknown. In this study, we used soluble recombi
nant extracellular domains of desmoglein 1 and desmoglein 3 to obtain affin
ity-purified anti-desmoglein 1 and anti-desmoglein 3 autoantibodies from pe
mphigus vulgaris sera and examined the pathogenicity of each fraction separ
ately using the passive transfer mouse model. By immunoprecipitation, the p
urified anti-desmoglein 1 and anti-desmoglein 3 showed no cross-reactivity.
The anti-desmoglein 1 autoantibodies in pemphigus vulgaris induced typical
pemphigus foliaceus lesions in neonatal mice, whereas the anti-desmoglein
3 fraction induced pemphigus vulgaris-like lesions. In addition, the pathog
enic anti-desmoglein 1 and anti-desmoglein 3 autoantibodies in pemphigus vu
lgaris had predominant IgG4 subclass specificity. These findings suggest th
at the anti-desmoglein 1 antibodies in pemphigus vulgaris are pathogenic.