Biomarker research in ARDS for predicting response to corticosteroid therapy

ARDS是一种危及生命的疾病，死亡率约为40%-60%。我们认为糖皮质激素是治疗ARDS的合理选择之一。转录因子T-bet由基因Tbx21编码，负责诱导T辅助(Th)1细胞和抑制来自初始T淋巴细胞的Th2细胞。到目前为止，只有一个常见的非同义Tbx21 SNP被描述，它编码用谷氨酰胺(H33Q)取代组氨酸33。Tantisira KG等人报道，Tbx21编码替换H33Q的非同义变异与哮喘儿童PC20(一种衡量呼吸道反应性的指标)的显著改善有关。此外，Tantisira KG等人还报道，与野生型H33H相比，Tbx21变异体H33Q增加了T辅助细胞1，降低了T辅助2细胞因子的表达。因此，Tbx21变种H33Q将具有改善呼吸道反应性的潜力。因此，在本研究中，我们认为Tbx21中的H33Q将被…MORE也是使用皮质类固醇后ARDS改善的预测指标。我们建立了一种限制性片段长度多态性(RFLP)方法来检测Tbx21基因H33Q对ARDS患者糖皮质激素治疗的影响。比较常见的非同义Tbx21单核苷酸多态与ARDS患者的临床结局和状态。对32例患者进行了Tbx21单核苷酸多态性分析。在32例患者中，25例(78%)在Tbx21基因上表现为H33H，6例(19%)表现为H33Q，1例(3%)表现为Q33Q。在H33Q/Q33Q组中，具有Tbx21基因功能变异的ARDS患者在接受某种皮质类固醇治疗后有可能表现出更好的疗效，此外，我们还发现了1例Tbx21基因Q33Q纯合子功能变异的病例。该病例显示了对皮质类固醇治疗的戏剧性药物遗传反应。应用糖皮质激素后PaO2/FiO2比值由49升至220，肺水肿明显改善。我们发现，具有Tbx21基因功能变异的ARDS患者，特别是Q33Q，在接受某种皮质类固醇治疗时有可能表现出更好的结果。较少

ARDS is a life threatening condition with mortality rates of about 40-60%. We thought that corticosteroids are one of logical choice for treatment of ARDS. A transcriptional factor T-bet, responsible for the induction of T helper (Th)1 cells and the repression of Th2 cells from naive T lymphocytes, is encoded by the gene TBX21. Only one common nonsynonymous TBX21 SNP has been described to date, which codes for a replacement of histidine 33 with glutamine (H33Q). Tantisira KG et al reported that the nonsynonymous variation in TBX21 coding for replacement of H33Q is associated with significant improvement in the PC20 (a measure of airway responsiveness) of asthmatic children. Additionally, Tantisira KG et al alsoreported the TBX21 variant H33Q increases T helper 1 and decreases T helper 2 cytokine expression comparably with wild type H33H. Hence, the TBX21 variant H33Q will have a potential to improve airway responsiveness. Therefore, herein this study, we thought that H33Q in TBX21 will … More also be a predictor for improvement in ARDS with the use of corticosteroids. We developed a Restriction Fragment Length Polymorphism(RFLP) method to examine influence of H33Q of the TBX21 gene to the therapy with corticosteroids in ARDS patients. The status of common nonsynonymous TBX21 SNP was compared with clinical outcome and status of ARDS patients. TBX21 SNP analysis was done in32 cases. Among the 32 patients, 25 (78%) patients showed H33H, 6 (19%) patients showed H33Q, and one patient (3%) showed Q33Q phenotype in the TBX21 gene. In the H33Q/Q33Q group, ARDS patients with functional variant in the TBX21 gene have a possibility to show better outcomes when they treated with some kind of corticosteroids.In addition, we found a case with homozygous functional variant of Q33Q of the TBX21 gene. The case shows dramatic pharmacogenetic response to the therapy with corticosteroids. The PaO2/FiO2 ratio increased from 49 to 220 and pulmonary edema clearly improved after administration of corticosteroids. We found ARDS patients with functional variants in the TBX21 gene, especially Q33Q, have a possibility to show better outcomes when they treated with some kind of corticosteroids. Less