PDF(Pubmed)
Abstract：
We investigated the potential of the point of sickling (PoS; the pO2 tension at which red cells start to sickle), determined by oxygen gradient ektacytometry to serve as a biomarker associated with the incidence of acute sickle cell disease-related complications in 177 children and 50 adults. In the pediatric cohort, for every 10 mmHg increase in PoS reflecting a greater likelihood of sickling, the likelihood of an individual experiencing >1 type of acute complication increased; the adjusted odds ratio (aOR) was 1.65. For every 0.1 increase in minimum elongation index (EImin; reflecting improved red blood cell deformability at hypoxia), the aOR was 0.50. In the adult cohort, for every 10 mmHg increase in PoS, we found an aOR of 3.00, although this was not significant after correcting for multiple testing. There was a trend for an association between higher PoS and greater likelihood of vaso-occlusive episodes (VOEs; children aOR, 1.35; adults aOR, 2.22). In children, only EImin was associated with VOEs (aOR, 0.68). When data of both cohorts were pooled, significant associations with PoS and/or EImin were found for all acute complications, independently and when >1 type of acute complication was assessed. These findings indicate that oxygen gradient ektacytometry generates novel biomarkers and provides a rationale for further development of these biomarkers in the assessment of clinical severity, evaluation of novel therapies, and as surrogate clinical trial end points. These biomarkers may be useful in assessing efficacy of novel therapies like pyruvate kinase activators, voxelotor, and L-glutamine.
摘要：
■我们研究了镰状点的潜力（PoS;红细胞开始镰状的pO2张力），在177名儿童和50名成人中，通过氧梯度ektacytometry测定作为与急性镰状细胞疾病相关并发症发生率相关的生物标志物。在儿科队列中，PoS每增加10mmHg，反映出镰状病的可能性更大，个体出现>1种急性并发症的可能性增加;校正比值比(aOR)为1.65.最小伸长指数每增加0.1(EImin;反映缺氧时红细胞变形能力改善),AOR为0.50。在成人队列中，PoS每增加10mmHg，我们发现aOR为3.00,尽管在校正多重检验后这并不显著.TherewasatendforanassociationbetweenhigherPoSandgreaterlikelyofvaso-culsiveplaces(VOEs;childrenaOR,1.35；成年人，2.22).在儿童中，只有EImin与VOE(AOR，0.68)。当两个队列的数据汇总时，发现所有急性并发症与PoS和/或EImin显著相关，独立地和当>1种急性并发症时进行评估。这些发现表明，氧梯度ektacytometry产生新的生物标志物，并为进一步发展这些生物标志物在临床严重程度的评估提供了理论基础。对新疗法的评估，并作为替代临床试验终点。这些生物标志物可用于评估丙酮酸激酶激活剂等新疗法的疗效。voxelotor,和L-谷氨酰胺.
