The humanized SCID mouse model to study HLA class II-linked autoimmunity to desmoglein 3 in pemphigus vulgaris

Background: Pemphigus vulgaris (PV) is a severe autoimmmune skin disorder induced by antibodies against desmoglein (Dsg) 3 on epidermal keratinocytes. Objectives: To establish an active animal model of PV to analyse the T-cell-regulated production of pathogenic antibodies in vivo. Methods: Immunodeficient SCID mice were injected with peripheral blood lymphocytes (PBL) from an HLA-DRB1*0402/DQ8+ patient with PV or a DRB1*0402/DQ8+ healthy donor, with or without subsequent injections of human Dsg3 or preincubation of PBL with Dsg3. Results: Human immunoglobulins (2.7-18.5 mg mL) were detected in all the mice after 8 weeks. Only one of 30 PBL-treated mice developed IgM against Dsg3 and showed intercellular IgM deposits in skin, nostrils and tongue. In contrast, in a previous study, 41% of SCID mice injected with PBL from patients with PV developed anti-Dsg3 antibodies in vivo. Conclusions: Our inability to reproduce these findings may be due to the transfer of slightly lower numbers of PBL (20 × 10 vs. 25-30 × 10).