Abstract
Introduction: Crohn’s disease (CD) is characterized by chronic and relapsing inflammation of the gastro-intestinal tract. It is assumed that oxidative stress contributes to CD pathogenesis, but systemic biomarkers for oxidative stress in CD are not yet identified. A reduction in free thiol groups in plasma proteins (“plasma free thiols”) reflects systemic oxidative stress since they are prime substrates for reactive oxygen species. Here, we determined the concentrations of plasma free thiols in CD patients and healthy controls and studied the putative correlation with disease parameters.Methods: Free thiols were quantified in plasma of patients with CD in clinical remission [according to the Harvey Bradshaw Index (HBI)] and healthy controls and adjusted for plasma albumin. Albumin-adjusted free thiol concentrations were analyzed for associations with clinical and biochemical disease markers.Results: Mean plasma free thiol concentrations were significantly lower in patients with CD (n = 51) compared to healthy controls (n = 27) (14.7 ± 2.4 vs. 17.9 ± 1.8 μmol/g albumin; P < 0.001). Patients with CD with above-average free thiols had significantly lower CRP levels (median 1.4 [interquartile range] [0.4; 2.6] vs. 3.6 [0.6; 7.0] mg/L; P < 0.05) and BMI (23.6 ± 4.8 vs. 27.1 ± 5.2 kg/m2; P < 0.05). Patients with CD having solely colonic disease demonstrated markedly reduced plasma free thiol concentrations compared to patients with ileocolonic involvement (13.2 ± 1.8 vs. 15.2 ± 2.2 μmol/g; P < 0.05). Finally, plasma free thiol concentrations negatively correlated with biomarkers of inflammation, including hsCRP, SAA, IL-17A (all P < 0.05), and VEGF.Conclusion: Plasma free thiols are reduced in patients with CD in clinical remission compared to healthy controls. Thus, subclinical CD disease activity is reflected by systemic oxidative stress and plasma free thiols may be a relevant therapeutic target and biomarker to monitor disease activity in CD.
Highlights
Crohn’s disease (CD) is characterized by chronic and relapsing inflammation of the gastro-intestinal tract
Accumulating evidence indicates that chronic intestinal inflammation in inflammatory bowel disease (IBD) is intimately associated with increased systemic levels of oxidative stress and enhanced reactive oxygen species (ROS) production, this evidence is predominantly derived from tissue analysis (Keshavarzian et al, 1992; Tanida et al, 2011; Zhu and Li, 2012; Pereira et al, 2015)
Plasma samples of 27 healthy, non-IBD controls were included for comparison, which were retrieved from a University Medical Center Groningen (UMCG) biobank containing pre-donation samples of living kidney donors [PSI-UMCG (IRB No 08/279)]
Summary
Crohn’s disease (CD) is characterized by chronic and relapsing inflammation of the gastro-intestinal tract. Crohn’s disease (CD) is an inflammatory bowel disease (IBD) characterized by chronic transmural intestinal inflammation that can affect any part of the gastro-intestinal tract (Sartor, 2008). IBD is characterized by chronic infiltration of various activated inflammatory cells, including polymorphonuclear cells, eosinophils and plasma cells (Kruidenier and Verspaget, 2002). Oxidative stress is characterized by increased production of reactive oxygen species (ROS). Accumulating evidence indicates that chronic intestinal inflammation in IBD is intimately associated with increased systemic levels of oxidative stress and enhanced ROS production, this evidence is predominantly derived from tissue analysis (Keshavarzian et al, 1992; Tanida et al, 2011; Zhu and Li, 2012; Pereira et al, 2015). The combination of excess ROS production and diminished antioxidant capacity might explain several pathophysiological aspects of CD (Alzoghaibi, 2013)
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