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糖抗原抗体与炎症性肠病病程的关系。

Association of Anti-glycan Antibodies and Inflammatory Bowel Disease Course.

机构信息

Laboratory of Immunology, University Hospital, Saint-Etienne, France.

Department of Gastroenterology, Lyon-Sud Hospital, Pierre-Benite, France and International Centre for Research in Infectiology [CIRI], Lyon, France.

出版信息

J Crohns Colitis. 2015 Jun;9(6):445-51. doi: 10.1093/ecco-jcc/jjv063. Epub 2015 Apr 19.

DOI:10.1093/ecco-jcc/jjv063
PMID:25895876
Abstract

BACKGROUND AND AIMS

The usefulness of anti-glycan antibodies alone or combined with anti-Saccharomyces cerevisiae [ASCA] or perinuclear antineutrophil cytoplasmic [pANCA] antibodies for diagnosis of inflammatory bowel disease [IBD], differentiation between Crohn's disease [CD] and ulcerative colitis [UC], disease stratification including IBD phenotype, and also for determination of the course of the disease, remain unclear.

METHODS

A large panel of serological anti-glycan carbohydrate antibodies, including anti-mannobioside IgG antibodies [AMCA], anti-chitobioside IgA [ACCA], anti-laminaribioside IgG antibodies [ALCA], anti-laminarin [anti-L] and anti-chitine [anti-C] were measured in the serum from a cohort of 195 patients with IBD] [107 CD and 88 UC]. The respective accuracy of isolated or combined markers for diagnosis, disease differentiation, stratification disease phenotype, and severity of the disease course, defined by a wide panel of criteria obtained from the past medical history, was assessed.

RESULTS

The positivity of at least one anti-glycan antibody was detected in a significant higher proportion of CD and UC compared with healthy controls [p < 0.0001 and p < 0.0007, respectively]. Whereas ASCA and ANCA antibody status had the highest efficacy to be associated with CD in comparison with UC (area under receiver operating characteristic curve [AUROC] = 0.70 for each], the adjunction of anti-laminarin antibody substantially improved the differentiation between CD and UC [AUROC = 0.77]. Titres of ACCA [> 51U/ml] and anti-laminarin [> 31U/ml] were significantly linked with a higher association with steroid dependency (odds ratio [OR] =2.0 [1.0-4.0], p = 0.03 and OR = 2.4 [1.1-5.2], p = 0.02, respectively]. We further defined the respective performance of anti-glycan antibodies to discriminate between patients with severe or not severe CD and UC course and determined the associated optimal cut-off values: severe CD course was significantly more likely in case of AMCA > 77U/ml [OR = 4.3; p = 0.002], ASCA > 63U/ml [OR = 3.5; p < 0.009] and at a lesser degree ACCA > 50U/ml [OR = 2.8; p < 0.02] and severe UC course was significantly associated with AMCA > 52U/ml [OR = 3.4; p = 0.04] and ACCA > 25U/ml [OR = 3.0; p < 0.04].

CONCLUSIONS

Anti-glycan antibodies are valuable serological markers, especially AMCA antibodies that may help clinicians to promptly classify patients into high risk for severe disease.

摘要

背景与目的

抗聚糖抗体单独或与抗酿酒酵母 [ASCA] 或核周抗中性粒细胞胞质 [pANCA] 抗体联合用于诊断炎症性肠病 [IBD]、区分克罗恩病 [CD] 和溃疡性结肠炎 [UC]、疾病分层包括 IBD 表型,以及确定疾病的进程,其有效性仍不清楚。

方法

在一组 195 名 IBD 患者[107 名 CD 和 88 名 UC]的血清中,我们检测了包括甘露糖基 IgG 抗体 [AMCA]、壳二糖 IgA [ACCA]、层粘连蛋白 IgG 抗体 [ALCA]、层粘连蛋白 [抗-L] 和壳素 [抗-C] 在内的大型糖基碳水化合物抗体血清学标志物面板。评估了单独或联合标志物在诊断、疾病区分、疾病表型分层、疾病严重程度方面的准确性,这些标志物的严重程度通过从过去的病史中获得的广泛标准来定义。

结果

与健康对照组相比,CD 和 UC 患者中至少有一种抗聚糖抗体阳性的比例显著更高[分别为 p < 0.0001 和 p < 0.0007]。与 UC 相比,ASCA 和 ANCA 抗体状态与 CD 的相关性最高(每个的受试者工作特征曲线 [ROC] 下面积 [AUROC] = 0.70),而添加抗层粘连蛋白抗体可显著提高 CD 和 UC 的区分度[AUROC = 0.77]。ACCA [> 51U/ml]和抗层粘连蛋白 [> 31U/ml]的滴度与更高的类固醇依赖性显著相关(比值比 [OR] =2.0 [1.0-4.0],p = 0.03 和 OR = 2.4 [1.1-5.2],p = 0.02)。我们进一步定义了抗聚糖抗体的各自性能,以区分严重或不严重的 CD 和 UC 病程,并确定了相关的最佳截断值:在 AMCA > 77U/ml [OR = 4.3;p = 0.002]、ASCA > 63U/ml [OR = 3.5;p < 0.009] 和 ACCA > 50U/ml [OR = 2.8;p < 0.02]的情况下,CD 严重程度显著更高,而严重 UC 病程与 AMCA > 52U/ml [OR = 3.4;p = 0.04]和 ACCA > 25U/ml [OR = 3.0;p < 0.04]显著相关。

结论

抗聚糖抗体是有价值的血清学标志物,尤其是 AMCA 抗体,可帮助临床医生快速将患者分类为患有严重疾病的高风险人群。

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