Abstract Background Redox imbalance and systemic oxidative stress are implicated in the pathophysiology of inflammatory bowel disease (IBD). Oxidative stress previously demonstrated strong associations with endoscopic disease activity in IBD1,2. In this study, we aimed to prospectively evaluate a panel of redox proteins, including circulating total free thiols (FTs), low-molecular-weight thiols including cysteine, glutathione (GSH), and homocysteine, ischemia-modified albumin (IMA), and thioredoxin-1, as biomarkers for endoscopic disease activity in patients with IBD. Methods Patients with IBD (n = 111) undergoing surveillance endoscopy were prospectively enrolled. Blood samples were collected at endoscopy along with clinical and biochemical disease activity assessments. Endoscopic disease activity was graded using the Mayo endoscopic subscore for patients with ulcerative colitis (UC) or the Simple Endoscopic Score for Crohn’s disease (SES-CD) for patients with Crohn’s disease (CD). Serum and plasma biomarkers (FTs, GSH, IMA, homocysteine, cysteine, thioredoxin-1) were measured by ELISA. Multivariable logistic regression analysis was used to investigate associations with disease activity, while adjusting for relevant confounders including sex, age and systemic steroid usage. Results Among all biomarkers, only serum GSH remained significantly associated with active endoscopic disease in multivariable analysis (adjusted odds ratio (OR) per doubling: 4.19, p = 0.04) (Fig. 1A). This was most evident in CD (p = 0.05), but not significant in UC (p = 0.10). IMA only showed a univariable association (p 0.05) (Fig. 1B). ROC analysis identified GSH as the most accurate oxidative stress marker in distinguishing quiescent from active endoscopic disease (AUC=0.71 in CD; 0.65 in UC) (Fig. 1C). All these biomarkers were individually outperformed by fecal calprotectin (AUC=0.77). However, combining calprotectin with these oxidative stress markers substantially improved discriminative capacity (AUC=0.95) (Fig. 1D). Conclusion Serum GSH may serve as a systemic biomarker of endoscopic disease activity in IBD, particularly in patients with CD. While less accurate than fecal calprotectin alone, systemic oxidative stress markers strongly enhance its diagnostic performance, suggesting complementary value for disease monitoring. References: 1. Bourgonje AR, Gabriëls RY, de Borst MH, Bulthuis MLC, Faber KN, van Goor H, Dijkstra G. Serum Free Thiols Are Superior to Fecal Calprotectin in Reflecting Endoscopic Disease Activity in Inflammatory Bowel Disease. Antioxidants (Basel). 2019 Sep 1;8(9):351. doi: 10.3390/antiox8090351. 2. Bohra A, Batt N, Dutt K, Sluka P, Niewiadomski O, Vasudevan A, Van Langenberg DR. Prospective Evaluation of Serum Free Thiols in Inflammatory Bowel Disease: A Candidate to Replace C-Reactive Protein for Disease Activity Assessment? Inflamm Bowel Dis. 2025 Feb 6;31(2):476-484. doi: 10.1093/ibd/izae069. Conflict of interest: Mr. Geertsema, Sem: This work was supported by a research grant from the De Cock-Hadders Foundation (to S.G.). The funders had no role in study design, data collection and analysis, preparation of the manuscript or decision to publish. Holstein, Hannah: No conflict of interest Bulthuis, Marian L. C.: No conflict of interest de Jong, Sofie: No conflict of interest Reinders-Luinge, Marjan: No conflict of interest Koerts-Steijn, Karin: No conflict of interest Muller Kobold, Anneke: No conflict of interest Faber, Klaas-Nico: K.N.F has received a grant from Janssen Pharmaceuticals, outside the submitted work. van Goor, Harry: H.v.G. has received a grant from Janssen Pharmaceuticals, outside the submitted work Dijkstra, Gerard: Grant: Royal DSM Personal Fees: Consultancy fee from Astra-Zeneca and Speakers fee from Abbvie Bourgonje, Arno R.: A.R.B. received speaker’s fees from AbbVie and Ferring, outside the submitted work.
Geertsema et al. (Thu,) studied this question.