Anti–Envoplakin Antibodies

Autoimmune blistering diseases are organ-specific autoimmune conditions characterised by autoantibodies against structural skin proteins. They are divided into four main groups depending on target antigens and clinical presentation: pemphigoid diseases, pemphigus diseases—including epidermolysis bullosa acquisita (EBA)—paraneoplastic pemphigus, and dermatitis herpetiformis (DH).

Diagnosis and differentiation of autoimmune blistering diseases rely on clinical assessment combined with the detection of autoantibodies against specific target antigens.

Pemphigus diseases can be classified clinically and immunopathologically into four different forms:

• Pemphigus foliaceus
• Pemphigus vulgaris
• IgA pemphigus
• Paraneoplastic pemphigus

Paraneoplastic pemphigus (PNP) is a potentially life-threatening intraepidermal blistering disease that can occur at any age. It is considered distinct from pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Skin lesions in PNP are polymorphic, combining features of PV with erythema multiforme–like changes, and are typically accompanied by severe stomatitis or other mucosal involvement. PNP is linked with underlying malignancy – haematologic neoplasms in ~84% of cases – and may also be associated with sarcoma.

In PNP, autoantibodies target desmosomal (desmoglein 3, desmoplakin I and II, envoplakin, plectin, periplakin) and hemidesmosomal (BP230) proteins, and an unknown 170 kDa antigen.

Autoantibodies against envoplakin – an intracellular anchoring protein involved in cytoskeletal organisation and in the formation of cell junctions such as desmosomes – are considered important diagnostic markers for PNP, with a seroprevalence of approximately 80%. They are detected in less than 1% of patients with BP, PV, or PF.