Pemphigus vulgaris and its active disease mouse model

Pemphigus is an autoimmune disease of the skin and mucous membranes and is mediated by IgG autoantibodies against desmoglein (Dsg), a cadherin-type cell-cell adhesion molecule in desmosomes. Recently, an active disease mouse model of pemphigus vulgaris (PV) was generated with a unique approach using autoantigen knockout mice, in which selftolerance of the defective gene product is not acquired. This approach included the adoptive transfer of Dsg3-/- lymphocytes to Rag2-/- immunodeficient mice that express Dsg3- induced stable production of pathogenic anti-Dsg3 IgG for over 6 months and the phenotype of PV including oral erosion with the typical histology in recipient mice. Subsequently, AK and NAK series of anti-Dsg3 IgG monoclonal antibodies were developed from the PV model mice. These monoclonal antibodies showed pathogenic heterogeneity in blister formation, which is, at least in part, explained by their epitopes, and synergistic pathogenic effects by combining several monoclonal antibodies reacting in different parts of the molecule. Although this model does not reflect the actual triggers of autoimmune diseases, it does provide a means to investigate the roles of T and B lymphocytes in perpetuating autoantibody production and to clarify unsolved immunological mechanisms in the autoimmune diseases.