Propionibacterium acnes catalase induces increased Th1 immune response in sarcoidosis patients

Respir Investig. 2015 Jul;53(4):161-9. doi: 10.1016/j.resinv.2015.02.005. Epub 2015 May 23.

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).

Conclusion: These results suggest that P. acnes KAT is an antigen that provokes allergic Th1 immune responses in sarcoidosis patients.

Keywords: Arginine deiminase; ELISA; Enzyme-linked immunospot assay; UDP-N-acetylglucosamine pyrophosphorylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antigens, Bacterial / immunology*
  • Catalase / immunology*
  • Catalase / isolation & purification
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Hypersensitivity / immunology*
  • Male
  • Mice
  • Middle Aged
  • Propionibacterium acnes / enzymology*
  • Propionibacterium acnes / immunology*
  • Sarcoidosis / immunology*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Th1 Cells / immunology*

Substances

  • Antigens, Bacterial
  • Catalase