title: Clinical and immunological profiles of anti-BP230-type bullous pemphigoid: Restriction of epitopes to the C-terminal domain of BP230, shown by novel ELISAs of BP230-domain specific recombinant proteins.
abstract: OBJECTIVE
  To confirm that sera from some BP patients reactive exclusively to the BP230 and to study the clinical and immunological characteristics of this condition.
  
  
  METHODS
  BP patients were divided into three groups: BP reactive only to BP230 (BP230-BP), BP reactive to both BP180 and BP230 (BP180-BP230-BP) and BP reactive only to BP180 (BP180-BP), based on the results of standard ELISAs for BP180 and BP230. Clinical features were statistically analyzed among the three groups. Then, targeted epitopes in each group were studied by immunoblotting and novel ELISAs using three domain-specific BP230 recombinant proteins.
  
  
  RESULTS
  Forty-one, 65 and 47 of 153 BP patients were categorized as BP230-BP, BP180-BP230-BP and BP180-BP, respectively. Clinically, BP230-BP patients showed significantly lower severity, less need of systemic steroids and better responses to various treatments, suggesting that BP230-BP is a milder condition. Immunoblotting and ELISAs of domain-specific BP230 recombinant proteins indicated that, while BP180-BP230-BP sera reacted with all three domains of BP230, BP230-BP sera reacted more frequently with epitopes in the BP230 C-terminal domain.
  
  
  CONCLUSIONS
  We propose a new disease entity, named anti-BP230-type BP, in which anti-BP230 antibodies might be pathogenic and react specifically with the BP230 C-terminal domain. While anti-BP230 antibodies in BP180-BP230-BP seem to be produced via intermolecular epitope spreading, anti-BP230 antibodies in BP230-BP are considered to be produced by different mechanisms.
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan, Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Aichi, Japan.
authors.forename: Taihei
authors.initials: T
authors.lastname: Hayakawa
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Kwesi
authors.initials: K
authors.lastname: Teye
authors.affiliation: Antibody Engineering Department/Manufacturing Division.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hachiya
authors.affiliation: Clinical Development Department/Business Development Division.
authors.forename: Rie
authors.initials: R
authors.lastname: Uehara
authors.affiliation: Marketing & Technical Support Department, Medical & Biological Laboratories Co. LTD., Nagoya, Aichi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hashiguchi
authors.affiliation: Department of Dermatology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors.forename: Tamihiro
authors.initials: T
authors.lastname: Kawakami
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Atsunari
authors.initials: A
authors.lastname: Tsuchisaka
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohara
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Sogame
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koga
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hamada
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Ohata
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Minao
authors.initials: M
authors.lastname: Furumura
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Norito
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Aichi, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Fukano
authors.affiliation: Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Aichi, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shimozato
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D000071821:Dystonin / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D024041:Non-Fibrillar Collagens / Q000276:immunology*; D010391:Pemphigoid, Bullous / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000097805:Collagen Type XVII
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D000071821:Dystonin; D000939:Epitopes; D024041:Non-Fibrillar Collagens; D011994:Recombinant Proteins; D000097805:Collagen Type XVII; C486268:DST protein, human
keywords: BP230; ELISA; autoantigen; bullous pemphigoid; epitope spreading; immunoblotting