Persistent elevation of serum LBP, IL-23 and IL-6 in infliximab-maintained Crohn's disease: a case–control study from Iraq with the serum LBP/albumin ratio as a novel composite biomarker
TL;DR
Serum LBP, IL-23 and IL-6 are markedly elevated in Iraqi CD patients and remain elevated during IFX maintenance, suggesting residual subclinical inflammation not captured by CRP alone.
Abstract
Background and aims Serum biomarkers that track mucosal inflammation in Crohn's disease (CD) beyond C-reactive protein (CRP) remain limited, particularly in Middle Eastern populations and in patients maintained on infliximab (IFX). We evaluated serum lipopolysaccharide-binding protein (LBP), interleukin-23 (IL-23) and interleukin-6 (IL-6) in active and IFX-maintained Iraqi CD patients versus healthy controls, and investigated the LBP-to-albumin ratio (LBP/Alb) as a novel composite biomarker. Methods In this cross-sectional case–control study (27 October 2025–25 March 2026) at Al-Najaf Gastrointestinal Tract Hospital, Iraq, 117 adults were enrolled: active CD (n = 32), IFX-CD (≥ 12 months maintenance; n = 35) and healthy controls (HC; n = 50). Serum LBP, IL-23 and IL-6 were measured by ELISA (BT Lab, Shanghai); CRP and albumin were measured on an SMT-120 analyser (Seamaty) in fixed-time mode. Activity was scored by the Harvey–Bradshaw Index (HBI); nutritional risk by MUST. Results LBP, IL-23 and IL-6 were significantly higher in both active CD and IFX-CD than in HC (all P < 0.001 after Bonferroni adjustment); pairwise differences between active CD and IFX-CD were not significant. IL-6 (AUC 0.982) and IL-23 (AUC 0.969) outperformed CRP (AUC 0.667) for discriminating all CD from HC. A combined IL-23 + IL-6 + CRP model reached AUC 0.995 (McFadden To address the possibility of overfitting and optimism in the diagnostic estimates, ROC performance was additionally evaluated by 5-fold stratified cross-validation in which standardisation and model fitting were performed within each training fold and applied to the held-out fold; cross-validated AUCs are reported with bootstrap 95% confidence intervals. Given the case–control design and the single-centre sample, these internal estimates are not a substitute for external validation, which remains necessary before any diagnostic application.R2 = 0.812). LBP/Alb correlated most strongly with HBI (ρ = 0.41), MUST (ρ = 0.50) and BMI (ρ = −0.46; all P < 0.001). Conclusions Serum LBP, IL-23 and IL-6 are markedly elevated in Iraqi CD patients and remain elevated during IFX maintenance, suggesting residual subclinical inflammation not captured by CRP alone. The LBP/Alb ratio is a promising accessible composite biomarker integrating bacterial-translocation and nutritional signals.