Antidesmoglein

Antidesmoglein refers to autoantibodies directed against desmoglein proteins, which are cadherin-type cell adhesion molecules in desmosomes that hold keratinocytes together in the epidermis and mucosal epithelia. The principal targets are desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3). Anti-Dsg1 and anti-Dsg3 antibodies are most notably associated with pemphigus diseases: pemphigus foliaceus is typically linked to anti-Dsg1, while pemphigus vulgaris often involves anti-Dsg3 and, in many cases, anti-Dsg1. The antibody profile helps explain the distribution of lesions, with mucosal involvement more common when anti-Dsg3 predominates.

Diagnosis relies on serology and immunofluorescence. Enzyme-linked immunosorbent assays (ELISAs) detect circulating anti-Dsg1 and anti-Dsg3 antibodies and often correlate with disease activity, aiding monitoring and treatment decisions. Indirect immunofluorescence on substrates such as monkey esophagus or human skin can reveal circulating desmoglein autoantibodies, while immunoblotting is used mainly in research settings.

Pathogenesis involves IgG autoantibodies binding desmogleins, disrupting desmosomal adhesion and causing acantholysis, the loss of intercellular connections that leads to intraepidermal blistering. The pathogenic IgG subclass is frequently IgG4, and disease activity may reflect antibody titer and specificity, with epitope spreading contributing to progression.

Treatment focuses on immunosuppression and control of autoantibody production. Standard regimens include systemic corticosteroids with steroid-sparing agents; rituximab, an anti-CD20 antibody, is increasingly used as frontline therapy in many cases. Monitoring anti-Dsg titers can help assess response and predict relapse.