Confirmation of a disease model of pemphigus vulgaris: characterization and correlation between disease parameters in...

Pemphigus vulgaris (PV) is a chronic autoimmune bullous disease associated with immunoglobulin G (IgG) autoantibodies against desmoglein 3 (Dsg3). Previously, a mouse model of PV was established by adoptive transfer of naive splenocytes from Dsg3(-/-) mice to Rag2(-/-) mice. The model is unique as Dsg3-specific naive lymphocytes from Dsg3(-/-) mice can be primed and activated by the endogenous Dsg3 in recipient mice, resulting in pathogenic anti-Dsg3 IgG without any active immunization. Here, we show that PV occurs after both intravenous (i.v.) and intraperitoneal (i.p.) transfer of naive splenocytes. We evaluated the robustness of the model by comparing engraftment as well as PV phenotype using several disease parameters. While engraftment of spleen cells was significantly better after i.p. transfer, anti-Dsg3 IgG antibody production, IgG deposition and disease score were comparable after both i.v. and i.p. cell transfer. Thus, transferred cells can be primed, activated and gain effector function. However, we detected heterogeneity in disease development, as only 46% of the mice developed hair loss, whereas 76% of the mice developed anti-Dsg3 IgG. We also tested cyclophosphamide in the model, as this drug is reported to be beneficial to PV patients. Cyclophosphamide significantly inhibited disease development in a preventive setting, and mice were free of symptoms 35 days after discontinuing the treatment. We have successfully confirmed the induction of PV after both i.v. and i.p. transfer. In addition, we have shown that this model can be used for evaluation of immunosuppressive drugs.