title: Epiplakin Is a Paraneoplastic Pemphigus Autoantigen and Related to Bronchiolitis Obliterans in Japanese Patients.
abstract: All plakin family proteins are known to be autoantigens in paraneoplastic pemphigus (PNP). In this study, we first examined whether PNP sera also react with epiplakin, another plakin protein, by various immunological methods using 48 Japanese PNP sera. Immunofluorescence confirmed that cultured keratinocytes expressed epiplakin. Epiplakin was detected by 72.9% of PNP sera by immunoprecipitation-immunoblotting with KU-8 cell extract, but not by immunoblotting of either normal human epidermal extract or KU-8 cell extract. Epiplakin was essentially not detected by 95 disease and normal control sera. Statistical analyses of various clinical and immunological findings revealed a significant correlation of the presence of anti-epiplakin antibodies with both bronchiolitis obliterans and mortality. No epiplakin-negative PNP case developed bronchiolitis obliterans. However, although 29.4% of European patients with PNP had bronchiolitis obliterans, significant correlation with anti-epiplakin autoantibodies was not observed. In further studies for lung, immunofluorescence showed the presence of epiplakin in normal human lung, particularly respiratory bronchiole, immunoprecipitation-immunoblotting showed that PNP sera reacted with epiplakin in cultured lung cells, and mice injected with polyclonal antibody specific to epiplakin histopathologically showed abnormal changes in small airway epithelia. These results indicated that epiplakin is one of the major PNP autoantigens and is related to PNP-related bronchiolitis obliterans.
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Fukuoka, 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, Fukuoka, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Numata
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Fukuoka, Japan.
authors.forename: Kwesi
authors.initials: K
authors.lastname: Teye
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Fukuoka, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Natsuaki
authors.affiliation: Department of Dermatology, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Tamihiro
authors.initials: T
authors.lastname: Kawakami
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Department of Dermatology, Oita University School of Medicine, Oita, Japan.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Oita University School of Medicine, Oita, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Department of Dermatology, Oita University School of Medicine, Oita, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Fukuoka, 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, Fukuoka, 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, Fukuoka, Japan.
authors.forename: Norito
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Shinzo
authors.initials: S
authors.lastname: Takamori
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.affiliation: Department of Dermatology, University Hospital Basel, Basel, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brandt
authors.affiliation: Center for Blistering Diseases, Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Hendri H
authors.initials: HH
authors.lastname: Pas
authors.affiliation: Department of Dermatology, Oita University School of Medicine, Oita, Japan.
authors.forename: Sakuhei
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Fukuoka, Japan. Electronic address: hashimot@med.kurume-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000368:Aged; D000818:Animals; D044466:Asian People / Q000706:statistics & numerical data; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D001989:Bronchiolitis Obliterans / Q000208:ethnology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D010257:Paraneoplastic Syndromes / Q000208:ethnology / Q000276:immunology* / Q000378:metabolism; D010392:Pemphigus / Q000208:ethnology / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D012016:Reference Values; D012494:Sampling Studies; D018709:Statistics, Nonparametric
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; C426678:epiplakin