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.


OBJECTIVE
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-1) 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 x 10(6) vs. 25-30 x 10(6)).
Rädisch
T
T
Department of Dermatology, RWTH Aachen, Germany.
Riechers
R
R
Hertl
M
M
D000818:Animals; D015551:Autoimmunity; D015820:Cadherins / Q000276:immunology*; D051184:Desmoglein 3; D004195:Disease Models, Animal; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D017710:Lymphocyte Transfusion; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D010392:Pemphigus / Q000276:immunology*
D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553506:HLA-DRB1*04:02 antigen; D007075:Immunoglobulin M