Dubinsky Marla C, Lin Ying-Chao, Dutridge Debra, Picornell Yoana, Landers Carol J, Farrior Sharmayne, Wrobel Iwona, Quiros Antonio, Vasiliauskas Eric A, Grill Bruce, Israel David, Bahar Ron, Christie Dennis, Wahbeh Ghassan, Silber Gary, Dallazadeh Saied, Shah Praful, Thomas Danny, Kelts Drew, Hershberg Robert M, Elson Charles O, Targan Stephan R, Taylor Kent D, Rotter Jerome I, Yang Huiying
Department of Pediatrics, Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Am J Gastroenterol. 2006 Feb;101(2):360-7. doi: 10.1111/j.1572-0241.2006.00456.x.
Crohn's disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients.
Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated.
Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5-80.4); p = 0.03). Pediatric CD patients positive for > or =1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03).
The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients.
克罗恩病（CD）是一种具有异质性的疾病，其特征为多种临床表型。儿童期发病的CD被描述为一种更具侵袭性的表型。遗传和免疫因素可能影响疾病表型和临床病程。我们研究了针对微生物抗原的免疫反应与疾病行为之间的关联，并前瞻性地确定了免疫反应性对儿科CD患者疾病进展的影响。
收集196例儿科CD病例的血清，检测免疫反应：使用酶联免疫吸附测定法检测抗I2、抗外膜蛋白C（抗OmpC）、抗CBir1鞭毛蛋白（抗CBir1）和抗酿酒酵母（ASCA）。评估免疫反应与临床表型之间的关联。
中位随访18个月后，58例患者（28%）出现肠内穿透和/或狭窄（IP/S）疾病。抗OmpC（p<0.0006）和抗I2（p<0.003）均与IP/S疾病相关。IP/S疾病的发生率随着免疫反应数量的增加而升高（p趋势=0.002）。在所有四种免疫反应均呈阳性的患者中，发生IP/S疾病的几率最高（比值比（95%置信区间）：11（1.5 - 80.4）；p = 0.03）。与所有免疫反应均呈阴性的患者相比，≥1种免疫反应呈阳性的儿科CD患者在诊断后更快进展为IP/S疾病（p<0.03）。
针对微生物抗原的免疫反应的存在及强度与CD患儿中更具侵袭性的疾病表型显著相关。这是第一项前瞻性研究，证明在存在免疫反应性的情况下，儿童发生疾病并发症的时间显著更快，从而预测儿科CD患者疾病进展为更具侵袭性的疾病表型。
