Pemphigus Desmoglein Antibodies

Pemphigus includes a group of often fatal autoimmune blistering diseases. Pemphigus vulgaris and its variants may present with oral or mucosal lesions alone or with mucosal plus skin lesions. Pemphigus foliaceous and variants present with skin lesions alone. Both forms of pemphigus are caused by autoantibodies to cell surface antigens on skin epithelium and mucous membranes.

The diagnosis of pemphigus depends on a combination of biopsy and serological studies. Skin biopsies of pemphigus vulgaris display acantholysis, suprabasal separation of the epithelium, and sparse inflammatory infiltrate. Direct immunofluorescence on a perilesional mucocutaneous biopsy displays intercellular deposition of IgG antibody and/or C3 complement along the epithelial cell surfaces. 

Originally, serum antibodies were detected by indirect immunofluorescence using human skin or monkey esophagus. The identification of the target antigens allowed for the development of highly sensitive and specific enzyme-linked immunosorbent assays.

Antibodies to desmoglein-1 (DSG1) and desmoglei- 3 (DSG3) have been shown to be present in patients with pemphigus.Desmoglein are calcium-dependent adhesion molecules in cell surface desmosomes. Many patients with pemphigus foliaceus have antibodies to DSG1. Patients with pemphigus vulgaris have antibodies to DSG3 and sometimes DSG1 as well.

Antibody titers correlate in a semiquantitative manner with disease activity. Patients with severe disease usually have high titers of antibodies to DSG. Titers usually decrease following response to treatment. 

Desmoglein antibodies are detected using a EuroImmun ELISA. Reference ranges for Desmoglein-1 and Desmoglein-3 antibodies is 0-20 RU/mL. 

References

Nousari HC, Anhalt GJ. Pemphigus and bullous pemphigoid. Lancet. 1999;354(9179):667-672.

Mihai S, Sitaru C. Immunopathology and molecular diagnosis of autoimmune bullous diseases. J Cell Mol Med. 2007;11(3):462-481.

Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell. 1991;67(5):869-877.

Koch PJ, Mahoney MG, Ishikawa H, et al. Targeted disruption of the pemphigus vulgaris antigen (desmoglein 3) gene in mice causes loss of keratinocyte cell adhesion with a phenotype similar to pemphigus vulgaris. J Cell Biol. 1997;137(5):1091-1102.

Ishii K, Amagai M, Hall RP, et al. Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. J Immunol. 1997;159(4):2010-2017.