Crohn's Disease in Clinical Remission Is Marked by Systemic Oxidative Stress

Arno R Bourgonje; Julius Z H von Martels; Marian L C Bulthuis; Marco van Londen; Klaas Nico Faber; Gerard Dijkstra; Harry van Goor

doi:10.3389/fphys.2019.00499

Crohn's Disease in Clinical Remission Is Marked by Systemic Oxidative Stress

Front Physiol. 2019 Apr 26:10:499. doi: 10.3389/fphys.2019.00499. eCollection 2019.

Authors

Arno R Bourgonje¹, Julius Z H von Martels¹, Marian L C Bulthuis², Marco van Londen³, Klaas Nico Faber¹, Gerard Dijkstra¹, Harry van Goor²

Affiliations

¹ Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
² Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
³ Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

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.

Keywords: Crohn’s disease; biomarker; disease activity; free thiols; oxidative stress; redox status.