title: Cloning and establishment of canine desmocollin-1 as a major autoantigen in canine pemphigus foliaceus.
abstract: Pemphigus foliaceus (PF) is the most common antibody-mediated autoimmune skin disease of dogs. Desmoglein-1 (DSG1), the major human PF antigen, represents only a minor autoantigen in canine PF (cPF). A recent immunomapping study proposed desmocollin-1 (DSC1) as a relevant candidate autoantigen for cPF. To investigate this hypothesis, 85 cPF sera were screened for the presence of anti-DSC1 IgG using indirect immunofluorescence (IIF) on live canine DSC1-transfected 293T cells. Seventy-five sera contained detectable antikeratinocyte IgG on IIF using footpad substrate (IIFpos cPF), while 10 did not (IIFneg cPF). Sera from 35 healthy dogs, eight from exfoliative superficial pyoderma (ESP)-affected dogs and 21 dogs with non-PF autoimmune blistering skin diseases served as controls. All sera were tested concurrently by IIF on canine DSG1-transfected as well as nontransfected cells. None of the healthy dog or ESP sera labelled any of the transfected or nontransfected cells. Fifty-seven of 75 IIFpos cPF (86%) and 7/10 of IIFneg cPF sera (70%) contained detectable anti-DSC1 IgG. None of these sera recognized nontransfected cells. Five cPF sera (6%) recognized DSG1 in addition to DSC1. Finally, 5/21 (24%) sera from dogs with non-PF autoimmune blistering diseases contained low anti-DSC1 IgG titers. In 7/10 dogs (70%), from whom serial serum samples were collected during treatment, anti-DSC1 IgG titers decreased in parallel with the reduction in disease clinical severity. Altogether, these findings suggest that DSC1 is a major autoantigen in cPF.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Bizikova
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Dean
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Thierry
authors.initials: T
authors.lastname: Olivry
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001483:Base Sequence; D015153:Blotting, Western / Q000662:veterinary; D003001:Cloning, Molecular; D051187:Desmocollins / Q000235:genetics / Q000276:immunology*; D004283:Dog Diseases / Q000097:blood / Q000276:immunology*; D004285:Dogs; D019084:Fluorescent Antibody Technique, Indirect / Q000662:veterinary; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008969:Molecular Sequence Data; D010392:Pemphigus / Q000097:blood / Q000276:immunology / Q000662:veterinary*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D001324:Autoantigens; D051187:Desmocollins; D007074:Immunoglobulin G; D012333:RNA, Messenger