细胞因子在移植相关移植物抗宿主病诊断中的作用

摘要

Objective To investigate the relationship between cytokines and human graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods In 21 patients undergoing allo-HSCT,the plasma concentrations of cytokines[soluble interleukin 2 receptor(sIL-2R), interferon-gama (IFN-γ), transforming growth factor-betal (TGF-β1)] were measured by using sandwich enzyme-linked immunological assay (ELISA) and the gene expressions of three cytokines were analysed by using semi-quantitate reverse transcriptase-polymerase chain reaction(RT-PCR). Results The concentrations and gene expressions of sIL-2R and IFN-γin the patients with GVHD were significantly higher than those without GVHD (P <0.01), and they were higher in the patients with aGVHD than with cGVHD and without GVHD(P <0.05); the levels of TGF-β1 in the patients with GVHD were significantly declined(P <0.01), but in those without aGVHD were obviously increased(P <0.05). After effective treatment, unnormal sIL-2R, IFN-γand TGF-β1 expressions recovered to the levels before transplantation. A multivariate COX analysis showed sIL-2R and TGF-β1 are independent prognostic factors for GVHD (P<0.001). Conclusion Monitoring the changes of sIL-2R, IFN-γand TGF-β1 expression levels (especially sIL-2R and TGF-β1) might provide predictive markers for GVHD after allo-HSCT. The sensitivity between RT-PCR and ELISA for detecting cytokines expressions had no difference.%目的 探讨异基因造血干细胞移植(allo-HSCT)后外周血细胞因子(CK)表达水平的变化及其与移植物抗宿主病(GVHD)的关系.方法 21例行allo-HSCT的血液病和实体瘤患者,根据预处理方案分为非清髓性(A组)和清髓性allo-HSCT组(B组);根据发生GVHD情况分为1组(A组发生aGVHD).2组(A组发生cGVHD),3组(B组发生aGVHD),4组(B组未发生GVHD),5组(A组未发生GVHD).采用半定量反转录聚合酶链反应(RT-PCR)和双抗体夹心酶联免疫吸附法(ELISA)对21例allo-HSCT患者动态监测外周血可溶性白细胞介素-2受体(sIL-2R)、干扰素-γ(IFN-γ)、转化生长因子β1(TGF-β1)表达变化情况.结果 21例患者均获得造血重建,A、B两组发生GVHD情况无差别(X2=3.711,P=0.144);RT-PCR方法及ELISA法检测CK,术后患者IL-2R、IFN-γ的表达均逐渐增高,IL-2R在+7天时已明显高于术前(P＜0.05),发生GVHD时达高峰,TGF-β1的表达随时间延长而逐渐降低,发生GVHD时最低;经治疗后,各指标逐渐接近术前水平;三指标在A组和B组表达不同(P＜0.01);发生GVHD组与无GVHD组相比,差异有统计学意义(P＜0.001).结论 sIL-2R、IFN-γ、TGF-β1可以作为allo-HSCT后预测aGVHD早期发生的指标;sIL-2R、TGF-β1独立于其他参数,更能影响GVHD发生;RT-PCR和ELISA两种方法检测CK的敏感性无差别.