Papp Maria, Sipeki Nora, Tornai Tamas, Altorjay Istvan, Norman Gary L, Shums Zakera, Roggenbuck Dirk, Fechner Kai, Stöcker Winfried, Antal-Szalmas Peter, Veres Gabor, Lakatos Peter Laszlo
Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Inova Diagnostics, San Diego, CA, USA.
J Crohns Colitis. 2015 Aug;9(8):659-68. doi: 10.1093/ecco-jcc/jjv087. Epub 2015 May 12.
Glycoprotein 2[GP2] and CUB zona pellucida-like domain 1[CUZD1] belong to protein families involved in gut innate immunity processes and have recently been identified as specific targets of anti-pancreatic autoantibodies [PAbs] in Crohn's disease[CD]. We aimed to determine the prognostic potential of novel target-specific PAbs regarding long-term disease course of an adult CD patient cohort.
Sera of 458 consecutive well-characterised IBD patients from a single referral IBD centre were tested by enzyme-linked immunosorbent assay [ELISA] with isoform 4 of recombinant GP2 [anti-MZGP2 and anti-GP2 IgA/IgG] and indirect immunofluorescence test [IIFT] system with GP2 and CUZD1 expressing transfected HEK 293 cells [anti-rPAg2 and rPAg1 IgA/IgG]. Clinical data were available on complicated disease or surgical interventions as well as disease activity and medical treatment during the prospective follow-up [median, 108 months].
Totals of 12.4% and 20.8% of CD patients were positive for IgA/IgG type of anti-GP2 and anti-CUZD1, respectively, with a significant difference compared with UC [p < 0.01]. Antibody status was stable over time. Agreement among three different anti-GP2 assays was good. Positivity for PAbs, mainly IgA subtypes, predicted a faster progression towards complicated disease course. In Kaplan-Meier analysis, time to surgery or development of perianal disease was associated with anti-GP2 IgA [pLogRank < 0.01] or anti-CUZD1 IgA [pLogRank < 0.001] positivity, respectively. Anti-CUZD1 IgA remained an independent predictor in the multivariate Cox-regression model (hazard ratio [HR]: 3.43, 95% confidence interval [CI]: 1.68-7.02, p < 0.001).
The present study has shown that specific PAbs [especially IgA subtype] predict complicated disease course including the development of perianal disease in CD.
糖蛋白2[GP2]和CUB透明带样结构域1[CUZD1]属于参与肠道固有免疫过程的蛋白家族，最近被确定为克罗恩病[CD]中抗胰腺自身抗体[PAbs]的特异性靶点。我们旨在确定新型靶点特异性PAbs对成年CD患者队列长期病程的预后潜力。
来自单一转诊IBD中心的458例连续且特征明确的IBD患者的血清，通过酶联免疫吸附测定[ELISA]检测重组GP2同工型4[抗MZGP2和抗GP2 IgA/IgG]，并通过间接免疫荧光试验[IIFT]系统检测表达GP2和CUZD1的转染HEK 293细胞[抗rPAg2和rPAg1 IgA/IgG]。在前瞻性随访期间[中位数为108个月]可获得关于疾病并发症或手术干预以及疾病活动和药物治疗的临床数据。
分别有12.4%和20.8%的CD患者抗GP2和抗CUZD1的IgA/IgG类型呈阳性，与溃疡性结肠炎[UC]相比有显著差异[p < 0.01]。抗体状态随时间保持稳定。三种不同抗GP2检测方法之间的一致性良好。PAbs阳性，主要是IgA亚型，预示着疾病向复杂病程发展得更快。在Kaplan-Meier分析中，手术时间或肛周疾病的发生分别与抗GP2 IgA[p对数秩< 0.01]或抗CUZD1 IgA[p对数秩< 0.001]阳性相关。抗CUZD1 IgA在多变量Cox回归模型中仍然是一个独立的预测因子（风险比[HR]：3.43，95%置信区间[CI]：1.68 - 7.02，p < 0.001）。
本研究表明，特异性PAbs[尤其是IgA亚型]可预测CD的复杂病程，包括肛周疾病的发生。
