Serum immune responses predict rapid disease progression among children with Crohn's disease: Immune responses predict disease progression
Serum immune responses predict rapid disease progression among children with Crohn's disease: Immune responses predict disease progression
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DOI：
10.1111/j.1572-0241.2006.00456.x
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发表时间：
2006-02-01
影响因子：
9.8
通讯作者：
Yang, HY
中科院分区：
文献类型：
--
作者：
Dubinsky, MC;Lin, YC;Yang, HY
背景与目的：克罗恩病（Crohn 'sdisease，CD）是一种异质性疾病，临床表现多样.儿童期发病的CD被描述为更具侵袭性的表型。遗传和免疫因素可能影响疾病的表型和临床过程。我们研究了微生物抗原的免疫反应与疾病行为的关联，并前瞻性地确定免疫反应对儿童CD patients.METHODS疾病进展的影响：收集了196例儿童CD患者的血清，并使用ELISA检测免疫反应：抗I2，抗外膜蛋白C（抗OmpC），抗CBir 1鞭毛蛋白（抗CBir 1）和抗酿酒酵母（ASCA）。免疫反应和临床表型之间的关联进行了evaluated.RESULTS：58例（28%）开发内部穿透和/或狭窄（IP/S）疾病后，平均随访18个月。抗OmpC（p < 0.0006）和抗I2（p < 0.003）均与IP/S疾病相关。IP/S疾病的频率随着免疫应答次数的增加而增加（p趋势= 0.002）。所有四种免疫应答均阳性的患者发生IP/S疾病的几率最高（OR（95% CI）：11（1.5-80.4）; p= 0.03）。与所有免疫反应阴性的儿童CD患者相比，免疫反应阳性>= 1的儿童CD患者在诊断后更快地进展为IP/S疾病（p < 0.03）。结论：对微生物抗原的免疫反应的存在和程度与CD儿童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的情况下，儿童发生疾病并发症的时间明显更快，从而预测儿童CD患者的疾病进展为更具侵袭性的疾病表型。
BACKGROUND AND AIM: 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.METHODS: 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.RESULTS: 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 >= 1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03).CONCLUSIONS: 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.