Gill Ryan M, Lee Tzong-Hae, Utter Garth H, Reed William F, Wen Li, Chafets Dan, Busch Michael P
Department of Laboratory Medicine, University of California, San Francisco, USA.
Blood. 2008 Apr 1;111(7):3880-3. doi: 10.1182/blood-2007-08-107144. Epub 2008 Jan 16.
Microchimerism (MC), defined as the persistence of allogeneic cells at low concentrations, is well documented in transfused trauma patients. We hypothesized that genetic polymorphisms linked to cytokine production could contribute to trauma-induced immune modulation and development of microchimerism after transfusion of trauma patients. We used high-throughput SYBR-green-based genotyping of single nucleotide polymorphisms (SNPs) to characterize 59 transfused trauma patients, with MC (n=30) and without MC (n=29), for 4 functionally significant SNPs: TNF (-308), IL 10 (-1082), IFNG (+874), and TGFB1 (+915). We then compared likelihood for development of MC and the magnitude of immune suppression among subjects with and without these selected immune response SNPs. We identified a significant association between TNF (-308A) SNP and both development of MC and diminished immune responsiveness. Hence predisposing genetic factors may explain, in part, why only a subset of trauma patients develops transfusion-associated microchimerism.
微嵌合体（MC）被定义为低浓度异体细胞的持续存在，这在输血创伤患者中已有充分记录。我们假设，与细胞因子产生相关的基因多态性可能有助于创伤诱导的免疫调节以及创伤患者输血后微嵌合体的形成。我们使用基于高通量SYBR绿的单核苷酸多态性（SNP）基因分型来对59例输血创伤患者进行特征分析，其中有微嵌合体（n = 30）和无微嵌合体（n = 29），检测4个功能上重要的SNP：TNF（-308）、IL 10（-1082）、IFNG（+874）和TGFB1（+915）。然后，我们比较了有和没有这些选定免疫反应SNP的受试者中微嵌合体形成的可能性以及免疫抑制的程度。我们发现TNF（-308A）SNP与微嵌合体的形成以及免疫反应性降低均存在显著关联。因此，易感遗传因素可能部分解释了为什么只有一部分创伤患者会发生输血相关微嵌合体。
