The anti-desmoglein 1 autoantibodies in pemphigus vulgaris sera are pathogenic

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.