Elevated Serum Protease 3 Antineutrophil Cytoplasmic Antibody in Mesalazine-Intolerant Ulcerative Colitis: A Potential Diagnostic Biomarker

美沙拉嗪不耐受性溃疡性结肠炎患者血清蛋白酶3抗中性粒细胞胞浆抗体升高:一种潜在的诊断生物标志物

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Abstract

Background/Objectives: Mesalazine agents are essential drugs for treating ulcerative colitis (UC). Biomarkers that can differentiate mesalazine intolerance from exacerbated UC are needed because of the similarity of their symptoms and increasing prevalence of mesalazine intolerance. The study aim was to assess the usefulness of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) to identify mesalazine intolerance in patients with UC. Methods: In this single-center retrospective study, patients with UC in whom serum PR3-ANCA was measured were included, and the serum levels were compared between the mesalazine-intolerant and -tolerant patient groups. The predictability of the marker to discriminate between these patients was analyzed. Results: Among 406 patients with UC with measured serum PR3-ANCA levels, 68 (17%) had mesalazine intolerance. The PR3-ANCA levels were significantly higher in the intolerance group than in the tolerance group [4.5 U/mL (0.8-26.2 U/mL) vs. 1.5 U/mL (0.0-8.5 U/mL), p = 0.001]. The area under the curve of the receiver operating characteristic curve analysis of the predictability of PR3-ANCA in differentiating mesalazine-intolerant patients from clinically active patients with UC was 0.755 (95% confidence interval: 0.634-0.876, cutoff value: 15.05 U/mL; sensitivity: 0.625, specificity: 0.813). Multivariate logistic regression analysis using various clinical factors revealed that serum PR3-ANCA > 15.0 U/mL was an independent risk factor of mesalazine intolerance (odds ratio: 8.25, 95% confidence interval: 2.52-27.02, p < 0.001). Conclusions: Serum PR3-ANCA could be a useful marker to identify mesalazine-intolerant patients with UC.

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