Multivariate modeling identifies neutrophil- and Th17-related factors as differential serum biomarkers of chronic murine colitis.

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  • Author(s): McBee ME;McBee ME; Zeng Y; Parry N; Nagler CR; Tannenbaum SR; Schauer DB
  • Source:
    PloS one [PLoS One] 2010 Oct 19; Vol. 5 (10), pp. e13277. Date of Electronic Publication: 2010 Oct 19.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Models, Biological*; Biomarkers/*blood ; Colitis/*blood ; Neutrophils/*metabolism ; Th17 Cells/*metabolism; Animals ; Chronic Disease ; Cytokines/blood ; Mice ; Mice, Knockout ; Multivariate Analysis ; Reactive Nitrogen Species/metabolism
    • Abstract:
      Background: Diagnosis of chronic intestinal inflammation, which characterizes inflammatory bowel disease (IBD), along with prediction of disease state is hindered by the availability of predictive serum biomarker. Serum biomarkers predictive of disease state will improve trials for therapeutic intervention, and disease monitoring, particularly in genetically susceptible individuals. Chronic inflammation during IBD is considered distinct from infectious intestinal inflammation thereby requiring biomarkers to provide differential diagnosis. To address whether differential serum biomarkers could be identified in murine models of colitis, immunological profiles from both chronic spontaneous and acute infectious colitis were compared and predictive serum biomarkers identified via multivariate modeling.
      Methodology/principal Findings: Discriminatory multivariate modeling of 23 cytokines plus chlorotyrosine and nitrotyrosine (protein adducts from reactive nitrogen species and hypochlorite) in serum and tissue from two murine models of colitis was performed to identify disease-associated biomarkers. Acute C. rodentium-induced colitis in C57BL/6J mice and chronic spontaneous Helicobacter-dependent colitis in TLR4(-/-) x IL-10(-/-) mice were utilized for evaluation. Colon profiles of both colitis models were nearly identical with chemokines, neutrophil- and Th17-related factors highly associated with intestinal disease. In acute colitis, discriminatory disease-associated serum factors were not those identified in the colon. In contrast, the discriminatory predictive serum factors for chronic colitis were neutrophil- and Th17-related factors (KC, IL-12/23p40, IL-17, G-CSF, and chlorotyrosine) that were also elevated in colon tissue. Chronic colitis serum biomarkers were specific to chronic colitis as they were not discriminatory for acute colitis.
      Conclusions/significance: Immunological profiling revealed strikingly similar colon profiles, yet distinctly different serum profiles for acute and chronic colitis. Neutrophil- and Th17-related factors were identified as predictive serum biomarkers of chronic colitis, but not acute colitis, despite their presence in colitic tissue of both diseases thereby demonstrating the utility of mathematical modeling for identifying disease-associated serum biomarkers.
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    • Grant Information:
      P01 CA026731 United States CA NCI NIH HHS; R01 DK055678 United States DK NIDDK NIH HHS; DK 55678 United States DK NIDDK NIH HHS
    • Accession Number:
      0 (Biomarkers)
      0 (Cytokines)
      0 (Reactive Nitrogen Species)
    • Publication Date:
      Date Created: 20101027 Date Completed: 20110307 Latest Revision: 20211020
    • Publication Date:
      20240628
    • Accession Number:
      PMC2957404
    • Accession Number:
      10.1371/journal.pone.0013277
    • Accession Number:
      20976045