ArticleTherapeutic advances in gastroenterology2026
Anti-TNF therapy attenuates the diagnostic utility of leucine-rich α2-Glycoprotein 1 for endoscopic activity in ulcerative colitis.
Article in Therapeutic advances in gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Serum leucine-rich α2-glycoprotein1 (LRG1) is a promising biomarker for mucosal inflammation in ulcerative colitis (UC). However, because systemic LRG1 expression is partly tumor necrosis factor-α (TNF-α)-dependent, anti-TNF therapy may pharmacologically suppress its levels independently of mucosal status. Objectives: To evaluate whether anti-TNF therapy is associated with false-negative serum LRG1 results, attenuates diagnostic accuracy for endoscopic activity (MES ≧ 2), and impairs diagnostic granularity to differentiate strict healing targets (MES 0 vs. 1) compared to other therapies. Design: A retrospective, single-center diagnostic accuracy study conducted in accordance with the STARD 2015 guidelines. Methods: We analyzed 127 paired colonoscopy-LRG1 evaluations (49 under anti-TNF, 78 without) from 50 patients receiving advanced therapies (April 2021-March 2025). Endoscopic activity was defined as Mayo Endoscopic Subscore (MES) ≥2. Diagnostic performance was evaluated using ROC analysis; AUC differences were compared using a cluster bootstrap approach. Factors associated with false-negative LRG1 (<16 μg/mL despite MES ≥2) were identified using generalized estimating equations. Results: Overall, LRG1 demonstrated satisfactory discrimination (AUC 0.81), but performed significantly lower under anti-TNF than non-anti-TNF therapy (AUC 0.44 vs. 0.91; ΔAUC=0.46). Among active evaluations, 45% (24/53) showed false-negatives. Anti-TNF was a strong independent predictor of false-negatives (OR 9.3, 95% CI 1.68-51.9), while JAK inhibitor use was protective (OR 0.09, 95% CI 0.01-0.80, P<0.03) with high accuracy (AUC 0.95 vs. 0.75, P<0.01). LRG1 failed to differentiate MES 0 and MES 1 in the anti-TNF cohort (p=0.63), whereas a marginal trend was observed in the non-anti-TNF cohort (p=0.06). Conclusion: Anti-TNF therapy may selectively attenuate serum LRG1 performance, potentially causing frequent false-negatives and obscuring the distinction between complete healing (MES 0) and mild residual inflammation (MES 1). Clinicians must consider the therapeutic context when interpreting LRG1 for disease monitoring.
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