Immunodiagnosis of pemphigus and mucous membrane pemphigoid

Abstract

Pemphigus and pemphigoid are two of a group of bullous diseases affecting oral mucosa and skin. Mucous membrane pemphigoid (MMP) comprises a heterogeneous group of disorders characterized by subepithelial separation and the deposition of immunoglobulins and complement along the basement membrane zone (BMZ). The target antigens in the epithelium and BMZ determine the nature of the condition, and recently there have been considerable improvements in our understanding of the BMZ antigenic composition. Pemphigus vulgaris (PV) is characterized by autoantibodies of the IgG isotype to the desmosomal glycoprotein desmoglein (Dsg) 3, whereas pemphigus foliaceus targets Dsg1, although at least 50% of PV patients have additional autoantibodies to Dsg1. The clinical phenotype appears to be determined by the relative amounts of Dsg1 and Dsg3. Patients with oral or mucosal PV have predominantly Dsg3 autoantibodies. The most frequently targeted antigen in MMP is bullous pemphigoid antigen 180 (BP180), although bullous pemphigoid antigen 230 (BP230), laminin 5, and beta 4 integrin are also involved. Circulating IgG and IgA antibodies may bind to different epitopes of BP180 - namely the NC16A domain or COOH-terminal domain. Pure ocular disease has been associated with IgA antibodies to a 45-kDa antigen and IgG antibodies to the 205-kDa antigen b4 integrin. The use of salt-split skin substrate enables differentiation between epidermal and dermal 'binders'. Since both the specificity and the antibody titer appear to have direct relationships with the disease severity, and a combination of clinical score and antibody titer provides valuable prognostic data, these investigations should be carried out on a more routine basis.