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血清学标志物检测在克罗恩病分型管理中的价值

Value of serological marker detection in hierarchical management of Crohn's disease

摘要:

目的 探讨血清学标志物在CD疾病表型诊断中的价值.方法 纳入2015年1月至2016年12月确诊为CD的100例患者,采用ELISA法检测其血清抗酿酒酵母抗体(ASCA)IgG、ASCAIgA、抗甘露二糖抗体(AMCA)、抗乙糖苷壳糖抗体(ACCA)、抗大肠埃希菌外膜C蛋白(OmpC)、抗荧光假单胞菌(I2)、抗鞭毛蛋白、核周型抗中性粒细胞胞质抗体(ANCA)、抗蛋白酶3等的表达水平.采用二元Logistic回归分析评估各血清学标志物与CD疾病表型的相关性,并采用ROC曲线评估其诊断价值.结果 抗I2与CD患者疾病类型为狭窄型显著相关(OR=34.304,P=0.011);ACCA和抗鞭毛蛋白与CD患者疾病类型为穿透型显著相关(OR=1.024,P=0.027;OR=2.702,P=0.021);ASCA IgA、AMCA与CD患者病变部位累及胃、十二指肠和小肠显著相关(OR=1.146,P=0.044;OR=1.035,P=0.013).在狭窄型CD的诊断中,抗I2的诊断准确度最高,AUC值为0.631(P=0.043),据此得出其最佳临界值(0.650),而后其敏感度升至28.6%(8/28).在穿透型CD诊断中,抗鞭毛蛋白的诊断准确度最高,AUC值为0.725(P<0.01),抗OmpC(AUC值为0.677,P=0.006)和ACCA(AUC值为0.644,P=0.025)也有较高的诊断准确度,据此得出以上三者的最佳临界值(0.395、0.225、59.500),而后其敏感度有提升;抗鞭毛蛋白、抗OmpC和ACCA组合任一项阳性诊断穿透型CD的AUC值为0.761(P<0.01),明显高于单抗体检测的诊断准确度.在病变部位累及胃、十二指肠和小肠的诊断中,AMCA的诊断准确度最高,AUC值为0.817(P<0.01),ASCA IgA(AUC值为o.772,P=0.001)和ACCA(AUC值为0.752,P=0.001)也具有较高的诊断准确度;ASCA IgA和AMCA任一项阳性的诊断CD病变部位累及胃、十二指肠和小肠的AUC值为0.905(P<0.01),明显高于单抗体检测的诊断准确度;ASCAIgA、AMCA和ACCA的最佳临界值分别为21,500、55.000和29.500,而后其敏感度有提升,三者中任一项阳性的敏感度也有提升.结论 血清学标志物检测对中国CD人群疾病表型的分型管理具有重要的临床价值.

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abstracts:

Objective To explore the values of serological markers in the phenotype diagnosis of Crohn's disease (CD).Methods From January 2015 to December 2016,100 patients diagnosed as CD were enrolled.The levels of human anti-Saccharomyces cerevisiae antibody (ASCA) IgG,ASCA IgA,anti-mannobioside carbohydrate antibody (AMCA),anti-chitobioside carbohydrate antibody (ACCA),antibody against outer membrane porin C of Escherichia coli (anti-OmpC),antibody against pseudomonas fluorescens (anti-I2),flagella protein antibody,perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and antibodies to proteinase-3 (anti-PR3) were detected by indirect enzyme-linked immunosorbent assay (ELISA).Binary Logistic regression analysis was used to analyze the correlation between the serological markers and the phenotype of CD.The diagnosis values were evaluated by receiver operating characteristic (ROC) curve.Results The level of anti-I2 was significantly correlated with the narrow type of patients with CD (odd ratios (OR) =34.304,P=0.011);ACCA and flagella protein antibody were significantly correlated with the penetrating type of patients with CD (OR =1.024,P=0.027;OR=2.702,P=0.021).ASCA IgA and AMCA were significantly correlated with the lesion involved gastric,duodenum and small intestine in CD patients (OR =1.146,P=0.044;OR=1.035,P=0.013).In the diagnosis of narrow type CD,the diagnostic accuracy of anti-I2 was the highest (area under curve (AUC) =0.631,P=0.043),and according to this result,its best cutoff value was 0.650,and then the sensitivity increased to 28.6% (8/28).In the diagnosis of penetrating type CD,the diagnostic accuracy of flagella protein antibody was the highest (AUC=0.725,P<0.01).Anti-OmpC (AUC =0.677,P=0.006) and ACCA (AUC=0.644,P=0.025) also had higher diagnostic accuracy.According to these results,the best cutoff values of flagella protein antibody,anti-OmpC and ACCA were 0.395,0.225 and 59.500,respectively,and then their sensitivity improved after correcting the cutoff values.The AUC of any one item positive in the combination of flagella protein antibody,anti-OmpC and ACCA in the diagnosis of penetrating type CD was 0.761 (P<0.01),which was significantly higher than the diagnostic accuracy of single antibody detection.In the diagnosis of the lesions involved gastric,duodenum and small intestine,the diagnostic accuracy of AMCA was the highest,and its AUC was 0.817 (P<0.01).ASCA IgA (AUC=0.772,P=0.001) and ACCA (AUC=0.752,P=0.001) also had higher diagnostic accuracy.The AUC of any one item positive of ASCA IgA and AMCA in the diagnosis of CD lesions involved gastric,duodenum and small intestine was 0.905 (P<0.01),which was significantly higher than the diagnostic accuracy of single antibody detection.The best cutoff values of ASCA IgA,AMCA and ACCA were 21.500,55.000 and 29.500,respectively.And their sensitivity improved after correcting the cutoff values.The sensitivity of any one item positive in the three items also improved.Conclusion The detection of serological markers has great clinical values in the hierarchical management of phenotypes in Chinese CD population.

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