Granulocyte Macrophage Colony-Stimulating Factor Auto-Antibodies and Disease Relapse in Inflammatory Bowel Disease
Granulocyte Macrophage Colony-Stimulating Factor Auto-Antibodies and Disease Relapse in Inflammatory Bowel Disease
复制标题
DOI：
10.1038/ajg.2013.360
复制
发表时间：
2013-12-01
影响因子：
9.8
通讯作者：
Foell, Dirk
中科院分区：
文献类型：
--
作者：
Daebritz, Jan;Bonkowski, Erin;Foell, Dirk
目的：沿着其他研究，我们报道了粒细胞巨噬细胞集落刺激因子（GM-CSF）的中和作用增加了肠道通透性和细菌移位，并减少了中性粒细胞细菌杀伤和抗微生物血清反应性。目的是探讨血清GM-CSF自身抗体（Ab）作为炎症性肠病（IBD）患者稳定缓解和预测复发的标志物的效用。方法：我们连续纳入181例成人和儿童克罗恩病（CD，n = 61）或溃疡性结肠炎（UC，n = 120）。在3年的时间里，我们在定期随访中收集了861份血清样本和610份粪便样本。结果：血清GM-CSF抗体水平与疾病活动性、部位和程度相关。复发前和复发后的时间过程分析显示，GM-CSF Ab浓度在临床复发前6个月明显增加。在1.7 μ g/ml（CD）和0.5 μ g/ml（UC）时，GM-CSF Ab预测2-6个月前复发的敏感性和特异性在CD中分别为88%和95%，在UC中分别为62%和68%。基线GM-CSF抗体水平>1.7 μ g/ml与CD在18个月内复发显著相关。结论：由于GM-CSF是骨髓细胞抗菌功能和对组织损伤的稳态反应所必需的，血清GM-CSF抗体水平可能反映肠通透性和细菌移位的程度。因此，GM-CSF Ab可能在早期阶段识别出有疾病复发风险的IBD患者，这使得该测试成为监测疾病活动和优化治疗的潜在工具。
OBJECTIVES: Along with others, we have reported that neutralization of granulocyte macrophage colony-stimulating factor (GM-CSF) increases intestinal permeability and bacterial translocation, and reduces neutrophil bacterial killing and anti-microbial seroreactivity. The objective was to investigate the utility of serum GM-CSF auto-antibody (Ab) as a marker for confirmation of stable remission and prediction of relapses in patients with inflammatory bowel disease (IBD).METHODS: We consecutively included 181 adults and children with Crohn's disease (CD, n = 61) or ulcerative colitis (UC, n = 120). Over a 3-year period, we collected 861 serum samples and 610 stool samples during regular follow-up visits. GM-CSF Abs and fecal S100 proteins were measured by an enzyme-linked immunoassay.RESULTS: Serum GM-CSF Ab levels correlated with disease activity, location, and extent. Time course analysis before and after relapse showed a clear increase of GM-CSF Ab concentrations up to 6 months before clinical relapse. At 1.7 mu g/ml (CD) and 0.5 mu g/ml (UC), the sensitivity and specificity of GM-CSF Ab for predicting relapse already 2-6 months earlier were 88 % and 95 % in CD and 62 % and 68 % in UC, respectively. A baseline GM-CSF Ab level of >1.7 mu g/ml was significantly associated with relapse of CD within 18 months.CONCLUSIONS: As GM-CSF is required for myeloid cell antimicrobial functions and homeostatic responses to tissue injury, serum GM-CSF Ab levels might reflect the degree of bowel permeability and bacterial translocation. Therefore, GM-CSF Ab might identify IBD patients at risk of disease relapse at an early stage, which makes the test a potential tool for monitoring disease activity and optimizing therapy.