Desmoglein-3 is a target autoantigen in spontaneous canine pemphigus vulgaris.
Pemphigus vulgaris (PV) is an autoimmune blistering skin disease of humans and companion animals. In human patients, PV is associated with the production of IgG autoantibodies specific for keratinocyte desmosomal glycoproteins of the cadherin family. The purpose of this study was to determine whether antikeratinocyte IgG autoantibodies were present in the skin and serum of dogs with PV, and also to identify the canine PV autoantigen(s) targeted by circulating autoantibodies. Eleven dogs were selected because of the microscopic demonstration of suprabasal epithelial acantholysis. Direct immunofluorescence revealed the presence of IgG autoantibodies bound to the membrane of keratinocytes in skin biopsy specimens of 8/9 dogs (89%). Using indirect immunofluorescence, serum-circulating IgG autoantibodies were found in 10/11 (91%) and 5/11 (45%) dogs, using normal canine gingiva and cultured canine oral keratinocytes, respectively. By immunoblotting using cultured canine oral keratinocyte protein lysates, IgG autoantibodies from 7/9 (78%) tested dogs recognized a 130-kDa antigen that comigrated with that identified by rabbit polyclonal antibodies raised against desmoglein-3. This 130 kDa antigen was confirmed to represent the canine equivalent of human desmoglein-3 by immunoprecipitation-immunoblotting. The results of these studies provide evidence that the canine desmoglein-3 homologue is a major autoantigen in dogs with PV. These observations further establish spontaneous canine PV as a natural model for research on pathogenesis, etiology and novel therapeutic approaches for this disease of humans.
Olivry
Thierry
T
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. Thierry_Olivry@ncsu.edu
Joubeh
Sohaila
S
Dunston
Stanley M
SM
Nishiyama
Takafumi
T
Ghohestani
Reza F
RF
D000818:Animals; D001324:Autoantigens / Q000302:isolation & purification; D015820:Cadherins / Q000276:immunology* / Q000302:isolation & purification; D002478:Cells, Cultured; D051184:Desmoglein 3; D004283:Dog Diseases / Q000276:immunology*; D004285:Dogs; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D019084:Fluorescent Antibody Technique, Indirect; D015151:Immunoblotting; D015603:Keratinocytes / Q000276:immunology; D008297:Male; D010392:Pemphigus / Q000276:immunology / Q000662:veterinary*
D001324:Autoantigens; D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3