Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, Kuwait City, Kuwait,
Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Acta Haematol. 2021;144(2):182-189. doi: 10.1159/000508521. Epub 2020 Sep 28.
Thrombospondin 1 (TSP-1) is a multifunctional glycoprotein secreted by platelets. In sickle cell disease (SCD), TSP-1 promotes red cell adhesion to the endothelium by binding to von Willebrand factor (vWF) and inhibiting its degradation by the protease ADAMTS-13. We investigated a possible correlation between TSP-1, vWF and ADAMTS-13 in adult and pediatric SCD patients.
Using commercially available ELISA kits, TSP-1, vWF and ADAMTS-13 levels were measured in 59 SCD patients (20 children and 39 adults) and compared with 59 age- and sex-matched controls. Associations between TSP-1 and parameters of interest were analyzed using Pearson's correlation coefficient.
Although TSP-1 levels were higher in adult and pediatric SCD patients than in controls, the increase was not statistically significant (p > 0.05). We found a significant positive correlation between TSP-1 and platelet count in both adult (r = 0.402, p = 0.01) and pediatric (r = 0.589, p = 0.01) patients, which is expected due to increased platelet activation in SCD. There was a positive correlation between TSP-1 and vWF in normal adults (r = 0.305, p = 0.049) and children (r = 0.633, p = 0.005) but not in patients (p > 0.05). A significant negative correlation between TSP-1 and ADAMTS-13 activity (r = -0.41, p = 0.01) was found in adult patients. Also, a significant negative correlation between TSP-1 and ADAMTS-13/vWF antigen ratio in both normal controls (r = -0.595, p = 0.009) and patients (r = -0.493, p = 0.032) is reported for the pediatric group.
Our findings confirm the inhibitory effects of TSP-1 on ADAMTS-13 activity in adult SCD patients. The negative correlation reported between TSP-1 and ADAMTS-13/vWF antigen ratio in pediatric subjects suggests a possible protective mechanism in younger individuals, although this is not related to the presence of SCD. This work emphasizes the impact of age on interpreting results related to the regulation of vWF expression and interaction with TSP-1 and ADAMTS-13 in SCD.
血小板分泌的多功能糖蛋白血栓反应蛋白 1（TSP-1）。在镰状细胞病（SCD）中，TSP-1 通过与 von Willebrand 因子（vWF）结合并抑制其被蛋白酶 ADAMTS-13 降解来促进红细胞与内皮细胞的黏附。我们研究了 TSP-1、vWF 和 ADAMTS-13 在成年和儿科 SCD 患者之间的可能相关性。
使用商业上可用的 ELISA 试剂盒，测量 59 例 SCD 患者（20 例儿童和 39 例成人）和 59 例年龄和性别匹配的对照者的 TSP-1、vWF 和 ADAMTS-13 水平。使用 Pearson 相关系数分析 TSP-1 与感兴趣参数之间的关联。
尽管成年和儿科 SCD 患者的 TSP-1 水平高于对照组，但差异无统计学意义（p>0.05）。我们发现，在成年（r=0.402，p=0.01）和儿科患者（r=0.589，p=0.01）中，TSP-1 与血小板计数呈显著正相关，这是由于 SCD 中血小板激活增加所致。在正常成年人（r=0.305，p=0.049）和儿童（r=0.633，p=0.005）中，TSP-1 与 vWF 之间存在正相关，但在患者中则无（p>0.05）。在成年患者中发现 TSP-1 与 ADAMTS-13 活性之间存在显著负相关（r=-0.41，p=0.01）。此外，在正常对照组（r=-0.595，p=0.009）和患者组（r=-0.493，p=0.032）中，TSP-1 与 ADAMTS-13/vWF 抗原比值之间存在显著负相关。
我们的发现证实了 TSP-1 在成年 SCD 患者中对 ADAMTS-13 活性的抑制作用。在儿科患者中，TSP-1 与 ADAMTS-13/vWF 抗原比值之间的负相关表明在年轻个体中可能存在一种保护机制，尽管这与 SCD 的存在无关。这项工作强调了年龄对解释与 SCD 中 vWF 表达的调控以及与 TSP-1 和 ADAMTS-13 相互作用相关的结果的影响。
