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

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...

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Autores principales: Bourgonje, Arno R., von Martels, Julius Z. H., Bulthuis, Marian L. C., van Londen, Marco, Faber, Klaas Nico, Dijkstra, Gerard, van Goor, Harry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497730/
https://www.ncbi.nlm.nih.gov/pubmed/31080419
http://dx.doi.org/10.3389/fphys.2019.00499
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author Bourgonje, Arno R.
von Martels, Julius Z. H.
Bulthuis, Marian L. C.
van Londen, Marco
Faber, Klaas Nico
Dijkstra, Gerard
van Goor, Harry
author_facet Bourgonje, Arno R.
von Martels, Julius Z. H.
Bulthuis, Marian L. C.
van Londen, Marco
Faber, Klaas Nico
Dijkstra, Gerard
van Goor, Harry
author_sort Bourgonje, Arno R.
collection PubMed
description 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/m(2); 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.
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spelling pubmed-64977302019-05-10 Crohn’s Disease in Clinical Remission Is Marked by Systemic Oxidative Stress Bourgonje, Arno R. von Martels, Julius Z. H. Bulthuis, Marian L. C. van Londen, Marco Faber, Klaas Nico Dijkstra, Gerard van Goor, Harry Front Physiol Physiology 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/m(2); 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. Frontiers Media S.A. 2019-04-26 /pmc/articles/PMC6497730/ /pubmed/31080419 http://dx.doi.org/10.3389/fphys.2019.00499 Text en Copyright © 2019 Bourgonje, von Martels, Bulthuis, van Londen, Faber, Dijkstra and van Goor. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Bourgonje, Arno R.
von Martels, Julius Z. H.
Bulthuis, Marian L. C.
van Londen, Marco
Faber, Klaas Nico
Dijkstra, Gerard
van Goor, Harry
Crohn’s Disease in Clinical Remission Is Marked by Systemic Oxidative Stress
title Crohn’s Disease in Clinical Remission Is Marked by Systemic Oxidative Stress
title_full Crohn’s Disease in Clinical Remission Is Marked by Systemic Oxidative Stress
title_fullStr Crohn’s Disease in Clinical Remission Is Marked by Systemic Oxidative Stress
title_full_unstemmed Crohn’s Disease in Clinical Remission Is Marked by Systemic Oxidative Stress
title_short Crohn’s Disease in Clinical Remission Is Marked by Systemic Oxidative Stress
title_sort crohn’s disease in clinical remission is marked by systemic oxidative stress
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497730/
https://www.ncbi.nlm.nih.gov/pubmed/31080419
http://dx.doi.org/10.3389/fphys.2019.00499
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