title: Integrin β4 is a major target antigen in pure ocular mucous membrane pemphigoid.
abstract: Previous studies of ocular mucous membrane pemphigoid (OMMP) have identified several components of the basement membrane zone to be autoantigens, including integrin β4. However, there are no extensive or definitive reported studies that address this, particularly in pure OMMP. To clarify the major autoantigens in pure OMMP. In this study, we examined sera from 43 pure OMMP patients for both IgG and IgA antibodies using newly developed immunoblotting analyses with a hemidesmosome-rich fraction and various recombinant proteins of integrin α6β4, in addition to our routine immune-serological tests. Using a hemidesmosome-rich fraction, sera from patients with pure OMMP demonstrated reactivity of IgG and/or IgA antibodies to integrin β4, BP180 and laminin-332. The reactivity of pure OMMP sera to integrin β4 was further confirmed by immunoblotting using integrin β4 recombinant proteins. Using concentrated supernatant of HaCaT cells, only one serum sample showed positive IgG and IgA reactivity to LAD-1, the ectodomain of BP180. None of the pure OMMP sera reacted with any autoantigens on immunoblotting using normal human epidermal or dermal extracts, or purified human laminin-332. Integrin β4 was considered to be the major and specific autoantigen for pure OMMP. The new methods established in this study are useful for detection of various autoantigens, particularly integrin β4.
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka.
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, Kurume, Fukuoka.
authors.forename: Hua
authors.initials: H
authors.lastname: Qian
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Sogame
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Aichi.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hirako
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsuruta
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka.
authors.forename: Norito
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka.
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, Kurume, Fukuoka.
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, Kurume, Fukuoka.
authors.forename: Zhexiong
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University School of Medicine, Kyoto, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Fukumoto
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University School of Medicine, Kyoto, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Sotozono
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University School of Medicine, Kyoto, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000276:immunology; D019084:Fluorescent Antibody Technique, Indirect; D022002:Hemidesmosomes; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D039663:Integrin beta4 / Q000276:immunology*; D024041:Non-Fibrillar Collagens / Q000276:immunology; D010390:Pemphigoid, Benign Mucous Membrane / Q000097:blood* / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D000097794:Kalinin; D000097805:Collagen Type XVII
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015815:Cell Adhesion Molecules; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D039663:Integrin beta4; D024041:Non-Fibrillar Collagens; D011994:Recombinant Proteins; D000097794:Kalinin; D000097805:Collagen Type XVII
keywords: autoantibody; autoantigen; hemidesmosome-rich fraction; integrin α6β4; pure ocular mucous membrane pemphigoid