Keslar Karen, Rodriguez E Rene, Tan Carmela D, Starling Randall C, Heeger Peter S
Department of Immunology, The Cleveland Clinic, Cleveland, OH, USA.
Transplantation. 2008 Nov 15;86(9):1319-21. doi: 10.1097/TP.0b013e3181889831.
Complement activation contributes to antibody-mediated allograft rejection, but increasing evidence also implicates complement proteins produced locally within the graft, in part by infiltrating mononuclear cells, as important mediators of tissue injury. To test this concept in transplant recipients, we evaluated complement, complement regulator, and T cell/proinflammatory marker gene expression by quantitative real-time polymerase chain reaction in 71 archived heart transplant biopsies and correlated the results with the histologic grade of rejection. Significantly more transcripts encoding alternative pathway components factor B, C3 and properdin, and C3a receptor and C5a receptor were detected in grade 3 versus grade 0 or 1 biopsies. The grade 3 rejections also contained significantly higher amounts of CD3, interferon gamma, perforin, and granzyme B genes. In addition to providing supportive evidence for a pathogenic role of graft-derived complement in human heart transplant injury, these correlations suggest that molecular profiling of complement gene expression could be useful in the diagnosis of human allograft rejection.
补体激活参与抗体介导的同种异体移植排斥反应，但越来越多的证据表明，移植组织内局部产生的补体蛋白（部分由浸润的单核细胞产生）是组织损伤的重要介质。为了在移植受者中验证这一概念，我们通过定量实时聚合酶链反应评估了71份存档的心脏移植活检组织中的补体、补体调节因子以及T细胞/促炎标志物基因表达，并将结果与排斥反应的组织学分级相关联。与0级或1级活检组织相比，在3级活检组织中检测到显著更多的编码替代途径成分B因子、C3和备解素以及C3a受体和C5a受体的转录本。3级排斥反应中还含有显著更高水平的CD3、干扰素γ、穿孔素和颗粒酶B基因。这些相关性不仅为移植来源的补体在人类心脏移植损伤中的致病作用提供了支持性证据，还表明补体基因表达的分子谱分析可能有助于人类同种异体移植排斥反应的诊断。
