IgG, IgA and IgE autoantibodies against the ectodomain of desmoglein 3 in active pemphigus vulgaris

Background IgG autoantibodies against desmoglein (Dsg) 3 play a key part in the pathogenesis of pemphigus vulgaris (PV), the most severe autoimmune bu llous disorder. Objectives To determine whether immunoglobulin isotypes other than IgG are detectable in the sera of patients with PV and whether a particular immunog lobulin subtype is associated with a distinct clinical phenotype of PV. Methods Sera from 41 patients with acute-onset, chronic active, and remitte nt PV disease with mucosal and cutaneous lesions were assayed against a bac ulovirus-expressed Dsg3 protein by immunoblot analysis. Results In acute-onset PV, Dsg3-reactive IgG1 was detected in nine of 15 (6 0%), IgG4 in 14 of 15 (93%), IgA in nine of 15 (60%) and IgE in two of 15 ( 13%) sera. In chronic active PV, Dsg3-reactive IgG1 was detected in 11 of 1 8 (61%), IgG4 in 16 of 18 (89%), IgA in 13 of 18 (72%) and IgE in two of 18 (11%) sera. In contrast, sera from patients with remittent PV disease cont ained only Dsg3-reactive IgG1 in six of eight (75%) and IgG4 in four of eig ht (50%) cases, but not Dsg3-reactive IgA or IgE. Conclusions In extension of previous findings, our study demonstrates that, in addition to IgG autoantibodies, IgA and occasionally IgE autoantibodies reactive with Dsg3 are present in acute and chronic active PV. The detecti on of Dsg3-reactive autoantibodies of the IgG4, IgA and IgE subclasses in a ctive PV provides additional evidence that PV is a T-helper 2-regulated aut oimmune disorder.