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针对患有克罗恩病和溃疡性结肠炎的儿童及青年进行抗中性粒细胞胞浆抗体(ANCA)、抗酿酒酵母抗体(ASCA)和抗OmpC抗体的血清学检测:诊断价值及与疾病表型的相关性

Serologic testing with ANCA, ASCA, and anti-OmpC in children and young adults with Crohn's disease and ulcerative colitis: diagnostic value and correlation with disease phenotype.

作者信息

Zholudev Anna, Zurakowski David, Young Wes, Leichtner Alan, Bousvaros Athos

机构信息

Inflammatory Bowel Disease Center, Division of Gastroenterology and Nutrition, Children's Hospital Boston, Boston, Massachusetts 02115, USA.

出版信息

Am J Gastroenterol. 2004 Nov;99(11):2235-41. doi: 10.1111/j.1572-0241.2004.40369.x.

Abstract

OBJECTIVES

Serologic testing is increasingly being utilized to evaluate children with suspected inflammatory bowel disease (IBD). The aim of this paper was to evaluate the sensitivity and specificity of a currently available panel involving four antibodies: deoxyribonuclease (DNase)-sensitive perinuclear antineutrophil cytoplasmic antibody (DNase-sensitive pANCA), IgA and IgG antibodies to Saccharomyces cerevisiae (IgA and IgG ASCA), and antibody to Escherichia coli outer membrane porin (anti-OmpC). We also wished to determine whether antibody levels correlated with disease activity, and whether a specific antibody pattern correlated with location and outcome of disease in children.

METHODS

We studied sera from 81 children with Crohn's disease (CD), 54 with ulcerative colitis (UC), and 63 controls. Clinical data, disease activity, and disease diagnosis were gathered at the time of serum sampling, and charts were re-reviewed at time of the study to determine long-term outcome. Enzyme-linked immunosorbent assay was utilized to determine titers of antibodies to ASCA, DNase-sensitive pANCA, and anti-OmpC; the presence of perinuclear staining for ANCA was confirmed by immunofluorescence.

RESULTS

We identified ASCA antibodies in 44% of CD patients, 0% of UC patients, and 1 control patient. DNase-sensitive pANCA antibodies were found in 70% of patients with UC, 18% of CD patients (predominantly Crohn's colitis), and 3% of controls. Anti-OmpC as an isolated assay had low sensitivity for both CD (24%) and UC (11%), and displayed a 5% false-positive rate. However, anti-OmpC did identify a small number of IBD patients not detected by the other assays. If any one or more of the four antibodies was positive, the overall sensitivity of the four antibody panel was 65% for CD and 76% for UC, with a specificity of 94%. Patients who were ASCA-positive were more likely to have disease of the ileum or ileum and right colon than patients who were ASCA-negative (58%vs 18%, p < 0.001). Patients with ASCA-positive were also more likely to require ileocecal resection (36%vs 13%, p < 0.05).

CONCLUSIONS

A currently available commercial antibody panel has good sensitivity and excellent specificity for CD and UC. The ASCA antibodies, while highly specific for CD, identify predominantly the subset of children with disease of the ileum and ascending colon who may be at increased risk of surgery.

摘要

目的

血清学检测越来越多地用于评估疑似炎症性肠病(IBD)的儿童。本文旨在评估目前可用的包含四种抗体的检测组合的敏感性和特异性:脱氧核糖核酸酶(DNase)敏感的核周抗中性粒细胞胞浆抗体(DNase敏感的pANCA)、抗酿酒酵母IgA和IgG抗体(IgA和IgG ASCA)以及抗大肠杆菌外膜孔蛋白抗体(抗OmpC)。我们还希望确定抗体水平是否与疾病活动相关,以及特定的抗体模式是否与儿童疾病的部位和结局相关。

方法

我们研究了81例克罗恩病(CD)患儿、54例溃疡性结肠炎(UC)患儿和63例对照的血清。在采集血清时收集临床数据、疾病活动情况和疾病诊断信息,并在研究时重新查阅病历以确定长期结局。采用酶联免疫吸附测定法测定ASCA、DNase敏感的pANCA和抗OmpC抗体的滴度;通过免疫荧光确认ANCA核周染色的存在。

结果

我们在44%的CD患者、0%的UC患者和1例对照患者中检测到ASCA抗体。在70%的UC患者、18%的CD患者(主要是克罗恩结肠炎)和3%的对照中发现了DNase敏感的pANCA抗体。单独检测抗OmpC对CD(24%)和UC(11%)的敏感性较低,假阳性率为5%。然而,抗OmpC确实识别出了一小部分其他检测未发现的IBD患者。如果四种抗体中的任何一种或多种呈阳性,四种抗体检测组合对CD的总体敏感性为65%,对UC为76%,特异性为94%。ASCA阳性的患者比ASCA阴性的患者更有可能患有回肠或回肠及右结肠疾病(58%对18%),p<0.001)。ASCA阳性的患者也更有可能需要进行回盲部切除术(36%对13%,p < 0.05)。

结论

目前可用的商用抗体检测组合对CD和UC具有良好的敏感性和出色的特异性。ASCA抗体虽然对CD具有高度特异性,但主要识别患有回肠和升结肠疾病、手术风险可能增加的儿童亚组。

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