Therapeutic advances in gastroenterology · 2026
Anti-TNF therapy attenuates the diagnostic utility of leucine-rich α2-Glycoprotein 1 for endoscopic activity in ulcerative colitis.
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Dejima Akihiro, Takatori Hajime, Miyazawa Masaki, Okafuji Hirofumi, Hayashi Tomoyuki, Seki Akihiro, Nio Kouki, Iida Noriho, Yamada Shinya, Shimakami Tetsuro, Toyama Tadashi, Yamashita Taro
Аннотация
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.
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.