Biomarkers in inflammatory bowel diseases: current status and proteomics identification strategies

Abstract

Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future development of preventive and treatment strategies. Thus, the clinical use of a panel of biomarkers represents a diagnostic and prognostic tool of potentially great value. The technological development in recent years within proteomic research (determination and quantification of the complete protein content) has made the discovery of novel biomarkers feasible. Several IBD-associated protein biomarkers are known, but none have been successfully implemented in daily use to distinguish CD and UC patients. The intestinal tissue remains an obvious place to search for novel biomarkers, which blood, urine or stool later can be screened for. When considering the protein complexity encountered in intestinal biopsy-samples and the recent development within the field of mass spectrometry driven quantitative proteomics, a more thorough and accurate biomarker discovery endeavor could today be performed than ever before. In this review, we report the current status of the proteomics IBD biomarkers and discuss various emerging proteomic strategies for identifying and characterizing novel biomarkers, as well as suggesting future targets for analysis.

Keywords: Biomarker; Citrullination; Crohn’s disease; Inflammatory bowel disease; Posttranslational modification; Proteomics; Ulcerative colitis.

Figure 1

Major increase is encountered in the proteome complexity, from genes to RNA transcripts and finally to the mature, often posttranslational modification modified, proteins (proteoforms).

Figure 2

Two commonly used mass spectrometry techniques. A: Matrix-assisted laser desorption/surface-enhanced laser desorption/ionizatio time of flight mass spectrometry (MS), where the peptide or protein sample is dried on a target plate. Subsequently, a laser is used to evaporate the dried sample, and the generated gas phase ions are analyzed by the mass spectrometer; B: Liquid chromatography (LC)-electrospray ionization (ESI) MS, where the liquid peptide (or protein) sample is separated on a LC column, and sequentially eluted often over several hours. The eluted peptides are injected directly into the mass spectrometer by ESI and analyzed.