title: Propionibacterium acnes catalase induces increased Th1 immune response in sarcoidosis patients.
abstract: BACKGROUND
  Propionibacterium acnes is one of the most commonly implicated etiologic agents of sarcoidosis. We screened antigenic proteins from this indigenous bacterium that increase Th1 responses in sarcoidosis patients.
  
  
  METHODS
  Antigenic bacterial proteins were screened by probing western blots of P. acnes whole cell lysates with blood plasma samples from 52 sarcoidosis patients and 34 healthy volunteers. Soluble protein antigens from the bands most frequently detected on blotting membranes were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Recombinant proteins were prepared from DNA sequences of the proteins identified by MALDI-TOF/MS and analyzed by immunologic assays.
  
  
  RESULTS
  MALDI-TOF/MS analysis identified propionyl-CoA carboxylase subunit beta, arginine deiminase (ADI), catalase (KAT), and UDP-N-acetylglucosamine pyrophosphorylase (UAP). Successfully prepared recombinant proteins from ADI, KAT, and UAP provoked humoral and cellular immune responses in mice immunized with P. acnes when measured by enzyme-linked immunosorbent assay for serum antibodies and enzyme-linked immunospot assay for interferon (IFN)-γ-secreting cells (ELISPOT IFN-γ assay) with lymph node cells. Plasma IgG and IgA titers to KAT and UAP were significantly higher in sarcoidosis patients than in healthy volunteers. When Th1 immune responses to ADI, KAT, and UAP were measured by ELISPOT IFN-γ assay with peripheral blood mononuclear cells from 12 sarcoidosis patients, 13 other pneumonitis patients, and 11 healthy volunteers, only the KAT protein provoked a significantly higher response in sarcoidosis patients (p=0.0032).
  
  
  CONCLUSIONS
  These results suggest that P. acnes KAT is an antigen that provokes allergic Th1 immune responses in sarcoidosis patients.
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan. Electronic address: p.yorozu.pth1@tmd.ac.jp.
authors.forename: Pariko
authors.initials: P
authors.lastname: Yorozu
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan. Electronic address: askapth1@tmd.ac.jp.
authors.forename: Asuka
authors.initials: A
authors.lastname: Furukawa
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan. Electronic address: uchida.path@tmd.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, Tokyo 113-8510, Japan. Electronic address: akashi.path@tmd.ac.jp.
authors.forename: Takumi
authors.initials: T
authors.lastname: Akashi
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan. Electronic address: kakepth1@tmd.ac.jp.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kakegawa
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan. Electronic address: ogawpth1@tmd.ac.jp.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Department of Clinical Engineering, School of Health Sciences, Tokyo University of Technology, Tokyo 144-8650, Japan. Electronic address: jminami@stf.teu.ac.jp.
authors.forename: Junko
authors.initials: J
authors.lastname: Minami
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan. Electronic address: y.suzuki.pth1@tmd.ac.jp.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan; Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan. Electronic address: awanobu0606@hotmail.co.jp.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Awano
authors.affiliation: Department of Integrated Pulmonology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan. Electronic address: hfurusawa.pulm@tmd.ac.jp.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Furusawa
authors.affiliation: Department of Integrated Pulmonology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan. Electronic address: miyazaki.pilm@tmd.ac.jp.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Integrated Pulmonology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan. Electronic address: ninase.pulm@tmd.ac.jp.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Inase
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8510, Japan; Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, Tokyo 113-8510, Japan. Electronic address: eishi.path@tmd.ac.jp.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D002374:Catalase / Q000276:immunology* / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011425:Propionibacterium acnes / Q000201:enzymology* / Q000276:immunology*; D012507:Sarcoidosis / Q000276:immunology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D002374:Catalase
keywords: Arginine deiminase; ELISA; Enzyme-linked immunospot assay; UDP-N-acetylglucosamine pyrophosphorylase