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.

Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System

“…145,146 The main source of citrulline, however, is the urea cycle, and alteration of urea production affects citrulline levels. 147 Furthermore, citrulline is a marker of a wide range of pathologies such as bowel diseases 148 and rheumatoid arthritis. 149 Hence, L-citrulline is not a specific biomarker of NO bioavailability and as such should not be used as an index of NO status.…”

Soluble Syndecan-1: Does This Biomarker Address a Seemingly Insoluble Problem in Inflammatory Bowel Disease?

“…Yet, the use of these invasive diagnostic procedures can be limiting with regard to monitoring disease activity and assessing disease severity during the treatment, recovery, and remission phases of the disease. There is therefore a need to identify new specific disease biomarkers that do not rely on invasive investigations for diagnosis [5][6][7][8][9].…”

Parallels Between Mammals and Flies in Inflammatory Bowel Disease

“…Two serological antibodies, perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) indicative of heightened immune response (Konrad et al 2004;Walker et al 2011) are certified as IBD diagnostic tools, however the number of biomarkers is rising (Meuwis et al 2007;Han et al 2013). Proteomic studies investigate biomarkers that aid in early diagnosis and classification of IBD through a selection of methodologies in sera, tissue and fecal samples (Bennike et al 2014). Such simple noninvasive tests could identify IBD and possibly help prognosis and the development of personalised treatments.…”