Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis
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 in...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2010
|
| Online Access: | http://hdl.handle.net/1721.1/60324 https://orcid.org/0000-0003-2673-5606 |
| _version_ | 1826203224775852032 |
|---|---|
| author | McBee, Megan E. Zheng, Yu Parry, Nicola Maria Anne Nagler, Cathryn R. Tannenbaum, Steven Robert Schauer, David B. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering McBee, Megan E. Zheng, Yu Parry, Nicola Maria Anne Nagler, Cathryn R. Tannenbaum, Steven Robert Schauer, David B. |
| author_sort | McBee, Megan E. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:33:18Z |
| format | Article |
| id | mit-1721.1/60324 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:33:18Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/603242022-09-28T08:33:18Z Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis McBee, Megan E. Zheng, Yu Parry, Nicola Maria Anne Nagler, Cathryn R. Tannenbaum, Steven Robert Schauer, David B. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Tannenbaum, Steven Robert McBee, Megan E. Zheng, Yu Parry, Nicola Maria Anne Tannenbaum, Steven Robert Schauer, David B. 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. National Institutes of Health (U.S) (P01 CA026731) National Institutes of Health (U.S) (DK 55678) MIT-Singapore Alliance. Research and Technology-Infectious Diseases 2010-12-20T14:00:20Z 2010-12-20T14:00:20Z 2010-10 2010-05 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/60324 McBee ME, Zeng Y, Parry N, Nagler CR, Tannenbaum SR, et al. (2010) Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis. PLoS ONE 5(10): e13277. doi:10.1371/journal.pone.0013277 https://orcid.org/0000-0003-2673-5606 en_US http://dx.doi.org/10.1371/journal.pone.0013277 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | McBee, Megan E. Zheng, Yu Parry, Nicola Maria Anne Nagler, Cathryn R. Tannenbaum, Steven Robert Schauer, David B. Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis |
| title | Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis |
| title_full | Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis |
| title_fullStr | Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis |
| title_full_unstemmed | Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis |
| title_short | Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis |
| title_sort | multivariate modeling identifies neutrophil and th17 related factors as differential serum biomarkers of chronic murine colitis |
| url | http://hdl.handle.net/1721.1/60324 https://orcid.org/0000-0003-2673-5606 |
| work_keys_str_mv | AT mcbeemegane multivariatemodelingidentifiesneutrophilandth17relatedfactorsasdifferentialserumbiomarkersofchronicmurinecolitis AT zhengyu multivariatemodelingidentifiesneutrophilandth17relatedfactorsasdifferentialserumbiomarkersofchronicmurinecolitis AT parrynicolamariaanne multivariatemodelingidentifiesneutrophilandth17relatedfactorsasdifferentialserumbiomarkersofchronicmurinecolitis AT naglercathrynr multivariatemodelingidentifiesneutrophilandth17relatedfactorsasdifferentialserumbiomarkersofchronicmurinecolitis AT tannenbaumstevenrobert multivariatemodelingidentifiesneutrophilandth17relatedfactorsasdifferentialserumbiomarkersofchronicmurinecolitis AT schauerdavidb multivariatemodelingidentifiesneutrophilandth17relatedfactorsasdifferentialserumbiomarkersofchronicmurinecolitis |