Longitudinal study of circulating protein biomarkers in inflammatory bowel disease

Emilie Viennois; Mark T Baker; Bo Xiao; Lixin Wang; Hamed Laroui; Didier Merlin

doi:10.1016/j.jprot.2014.09.002

Longitudinal study of circulating protein biomarkers in inflammatory bowel disease

J Proteomics. 2015 Jan 1:112:166-79. doi: 10.1016/j.jprot.2014.09.002. Epub 2014 Sep 16.

Authors

Emilie Viennois¹, Mark T Baker², Bo Xiao², Lixin Wang³, Hamed Laroui⁴, Didier Merlin³

Affiliations

¹ Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Chemistry Department, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; Veterans Affairs Medical Center, Decatur, GA, USA. Electronic address: eviennois@gsu.edu.
² Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Chemistry Department, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
³ Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Chemistry Department, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; Veterans Affairs Medical Center, Decatur, GA, USA.
⁴ Chemistry Department, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.

Abstract

Inflammatory bowel diseases (IBDs) are chronic and progressive inflammatory disorders of the gastrointestinal tract. In IBD, protein serological biomarkers could be relevant tools for assessing disease activity, performing early-stage diagnosis and managing the treatment. Using the interleukin-10 knockout (IL-10(-/-)) mouse, a model that develops a time-dependent IBD-like disorder that predominates in the colon; we performed longitudinal studies of circulating protein biomarkers in IBD. Circulating protein profiles in serum samples collected from 30-, 93-, to 135-day-old IL-10(-/-) mice were investigated using two-dimensional differential gel electrophoresis and MALDI-TOF/TOF tandem mass spectrometry. A total of 15 different proteins were identified and confirmed by ELISA and Western blot to be differentially accumulated in serum samples from mid- to late-stage IL-10(-/-) mice compared to early non-inflamed IL-10(-/-) mice. The use of another model of colitis and an extra-intestinal inflammation model validated this biomarker panel and demonstrated that comprised some global inflammatory markers, some intestinal inflammation-specific markers and some chronic intestinal inflammation markers. Statistical analyses using misclassification error rate charts validated the use of these identified proteins as powerful biomarkers of colitis. Unlike standard biomarker screening studies, our analyses identified a panel of proteins that allowed the definition of protein signatures that reflect colitis status.

Biological significance: Crohn's disease (CD) and ulcerative colitis (UC) are the most common inflammatory bowel diseases (IBDs) occurring in humans. The major current diagnosis tool is colonoscopy, which is invasive and could lead to false diagnosis. The emergence of serological biomarkers enables the use of new diagnosis tools such as protein signatures for IBD diagnosis/management. Using 2D-DIGE coupled to mass spectrometry, our longitudinal study in a mouse model of colitis identified a signature of protein biomarkers for specific stages of disease.

Keywords: 2D-DIGE; Diagnostics; IBD; Serological biomarkers; Therapeutics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Biomarkers / blood
Blood Proteins / metabolism*
Colitis, Ulcerative / blood*
Crohn Disease / blood*
Disease Models, Animal
Female
Mice
Mice, Knockout

Substances

Biomarkers
Blood Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding