中文摘要：

目的 探讨IL-2、IL-4、IL-18及IP10 4种细胞因子基因mRNA表达水平变化与急性移植物抗宿主病（aGVHD）发生的关系,尝试采用不同细胞因子组合的检测提高aGVHD诊断的准确率.方法 选取58例行异基因造血干细胞移植（allo-HSCT）患者,在移植后不同时间点取外周血有核细胞提取RNA,通过实时定量聚合酶链反应（RQ-PCR）检测IL-2、IL-4、IL-18及IP10 4种细胞因子基因mRNA的表达,结合临床病例特点研究其与aGVHD发生的关系.结果 IL-2和IL-18 mRNA表达在aGVHD发生时较植活时分别升高2.69倍和3.12倍（P=0.000和P=0.000）,二者在感染时mRNA的表达轻度上升,但与植活时相比差异无统计学意义（P=0.208和P=0.123）;IL-4和IP10 mRNA表达在aGVHD发生时较植活时有所下降,但差异无统计学意义（P=0.230和P=0.325）;IL-2和IL-18 mRNA表达作为单独指标对诊断aGVHD均有统计学意义（P=0.000和P=0.000）;利用Logistic回归分析IL-2、IL-18、IL-4和IP10表达水平的变化与aGVHD的关系,发现IL-2、IL-18和IL-4是与aGVHD密切相关的因子（β=1.13,P=0.068;β=1.339,P=0.047;β=-0.600,P=0.008）;在该模型中组合3种细胞因子可使诊断aGVHD的ROC曲线AUC达到0.862（95%CI：0.768～0.957,P=0.000）,与使用单一因子相比,可同时获得较高的敏感度（75.0%）和特异度（83.3%）.结论 与使用单一参数相比,利用多种细胞因子组合诊断aGVHD可进一步优化aGVHD的诊断.

英文摘要：

Objective To observe the relationship between variation of IL-2, IL-4, IL-18 and IP10 mRNA expressions in peripheral blood and the occurrence of acute graft-versus-host disease （aGVHD）, and investigate whether some cytokines combined expression profiles could improve the diagnostic accuracy of aGVHD. Methods A total of 58 patients who underwent allogeneic hematopoietic stem cell transplantation （aIIo-HSCT） were enrolled for the study. Peripheral blood samples were collected at different time points after transplantation. The mRNA expression levels of 4 kinds of eytokines （IL-2, IL-4, IL-18, IP10） were measured by real-time quantitative PCR（RQ-PCR）. The relationship between mBNA expression level and the occurrence of aGVHD was analyzed with clinieal features. Results The expression levels of IL-2 and IL-18 at the onset of aGVHD were mueh higher than those after engraftment, being 2.69-fold and 3.12-fold increase,respectively （P=0. 000 ＆ P=0. 000）. The expressions of IL-2 and IL-18 mRNAs were slightly increased in patients with infection, but not statistically significant （P=0.208 ＆ P=0. 123）. There was a slight but not statistically significant decrease of IL-4 and IP10 mRNA expressions at the onset of aGVHD （P =0.230 ＆P=0. 325）. Either IL-2 or IL-18 expression level could diagnose aGVHD as an independent factor （P=0.000 ＆ P = 0. 000 ）. The multivariate logistic regression analysis showed that the main factors related to aGVHD were IL-2, IL-18 and IL-4（β= 1. 13,P=0.068 ＆β=1.339,P=0.047 ＆β= -0. 600,P =0.008 respectively）. A composite panel of these three cytokines produeed a better model for the diagnosis of aGVHD （AUC： 0.862, 95%CI： 0.768 -0. 957, P=0.000）, and the sensitivity and specificity were 75.0% ＆ 83.3% respectively. Conclusion The diagnosis of aGVHD can be optimized with a composite cytokines panel.