Biomarker research in ARDS for predicting response to corticosteroid therapy

急性呼吸窘迫综合征是一种危及生命的疾病，死亡率约为40-60%。我们认为皮质类固醇是治疗ARDS的合理选择之一。一种转录因子T-bet由TBX21基因编码，负责诱导T辅助（Th）1细胞并抑制幼稚T淋巴细胞中的Th2细胞。迄今为止，只有一个常见的非同义TBX21 SNP被描述，它编码用谷氨酰胺替代组氨酸33 （H33Q）。Tantisira KG等人报道TBX21编码替代H33Q的非同义变异与哮喘儿童PC20（气道反应性指标）的显著改善相关。此外，Tantisira KG等人也报道了TBX21变体H33Q与野生型H33H相比，增加了辅助性T 1和降低了辅助性T 2细胞因子的表达。因此，TBX21改型H33Q将具有改善气道反应性的潜力。因此，在本研究中，我们认为TBX21中的H33Q也可能是使用皮质类固醇改善ARDS的预测因子。我们建立了限制性片段长度多态性（RFLP）方法来检测TBX21基因H33Q对ARDS患者皮质类固醇治疗的影响。比较常见非同义TBX21 SNP的状态与ARDS患者的临床结局和状态。32例进行TBX21 SNP分析。32例患者中，H33H 25例（78%），H33Q 6例（19%），TBX21基因Q33Q表型1例（3%）。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时，有可能表现出更好的结果。此外，我们还发现了一例TBX21基因Q33Q的纯合功能变异。该病例对皮质类固醇治疗表现出显著的药理学反应。给糖皮质激素后，PaO2/FiO2比值从49增加到220，肺水肿明显改善。我们发现，患有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。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