title: Cloning of hamster type XVII collagen cDNA, and pathogenesis of anti-type XVII collagen antibody and complement in hamster bullous pemphigoid.
abstract: Bullous pemphigoid is an inflammatory subepidermal blistering skin disease associated with an IgG autoimmune response to the type XVII collagen. The immunopathologic features of bullous pemphigoid can be reproduced in mice by the passive transfer of anti-type XVII collagen antibodies. In this model, it is thought that blister formation depends upon complement activation, neutrophil recruitment, and some proteolytic enzymes. In this study, we cloned hamster type XVII collagen cDNA, which contains a 4296 bp coding region and which is predicted to be a transmembrane protein with an extracellular collagenous domain, residing in type II orientation. Antipeptide antibodies (anti-1191 IgG) were obtained against a segment of hamster type XVII collagen homologous with the human type XVII collagen autoantibody-reactive site. The antipeptide antibodies were passively transferred to neonatal Syrian hamsters. The injected hamsters developed a microscopic subepidermal blister as seen previously in the mice. In order to test whether antigen-antibody complexes and complement initiate the subepidermal blister formation, we carried out experiments in vitro on condition that inflammatory cells were completely eliminated. Complement activation in sera was inhibited either by heating (at 56 degrees C for 30 min) or by preincubating with cobra venom factor. When the hamster skin was incubated with fresh anti-1191 antisera, separation of dermal-epidermal junction was observed. The anti-1191 IgG failed to induce C3 deposition and dermal-epidermal junction separation, however, if the anti-1191 IgG was added alone or complement activation in sera was inhibited. Under these conditions, IgG but not C3 was deposited on the basement membrane. These results strongly suggest that antigen-antibody complexes and complement initiate dermal-epidermal junction separation.
authors.affiliation: Division of Oncology and Biology, Genome Research Group, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Naokazu
authors.initials: N
authors.lastname: Inoue
authors.forename: Riako
authors.initials: R
authors.lastname: Masuda
authors.forename: Akira
authors.initials: A
authors.lastname: Fujimori
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Saito
authors.forename: Shinobu
authors.initials: S
authors.lastname: Imajoh-Ohmi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shinkai
authors.forename: Hisako
authors.initials: H
authors.lastname: Sakiyama
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D000906:Antibodies / Q000276:immunology*; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000917:Antibody Formation; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence / Q000235:genetics; D002352:Carrier Proteins; D003001:Cloning, Molecular; D003094:Collagen / Q000235:genetics* / Q000276:immunology*; D003165:Complement System Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D006224:Cricetinae; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000235:genetics*; D000071821:Dystonin; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000097805:Collagen Type XVII
chemical_list: D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003165:Complement System Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D000071821:Dystonin; D007106:Immune Sera; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human