PDF(Pubmed)
Abstract：
Sickle cell anemia (SCA) causes a long-standing vascular inflammation state, leading to endothelial dysfunction and chronic overexpression of several adhesion molecules, which contributes to acute and constant vaso-occlusive (VOC) episodes. It has been demonstrated that hydroxyurea (HU) can reduce VOC events, organ damage, blood transfusions, and even the adhesion properties to endothelial cells of SCA subjects. Due to VOC episodes, these patients are also more susceptible to recurrent bacterial translocation and dysbiosis. Given this, our study aimed to uncover the interplay between adhesion molecules, gut microbiome, and hydroxyurea in a population of Angolan SCA children. Serum and fecal samples were obtained before and after HU treatment in 35 children. After HU, four of these adhesion molecules were significantly reduced: sE-selectin (p = 0.002), ADAMTS13 (p = 0.023), sICAM-1 (p = 0.003), and sVCAM-1 (p = 0.018). A positive correlation was observed between the number of neutrophils and sICAM-1, platelets, and sP-selectin, and also between leukocytes, sICAM-1, and sVCAM-1. Most taxa showing a significant correlation mainly belonged to the Clostridiales order. Specifically, from the Clostridium genera, the groups g19, g21, and g34 were all negatively correlated with HbF levels; g19, g21, and g24 positively correlated with leukocytes; g19 positively with neutrophils and sVCAM-1; and g34 positively with E- and P-selectin. Serratia, an opportunistic pathogen, was positively correlated with sE-selectin and sICAM-1 levels. Additionally, a negative correlation was observed between sP-selectin and Bifidobacterium. Research studies in this area could improve our understanding and contribute to finding new prognostic biomarkers to guarantee precise SCA patient stratification and predict severe complications.
摘要：
镰状细胞性贫血（SCA）导致长期的血管炎症状态，导致内皮功能障碍和几种粘附分子的慢性过度表达，这有助于急性和持续的血管闭塞（VOC）发作。已经证明羟基脲（HU）可以减少VOC事件，器官损伤,输血,甚至SCA受试者对内皮细胞的粘附特性。由于VOC发作,这些患者也更容易反复发生细菌移位和菌群失调。鉴于此,我们的研究旨在揭示粘附分子之间的相互作用，肠道微生物组，安哥拉SCA儿童中的羟基脲。在HU治疗前后获得了35名儿童的血清和粪便样本。在HU之后,这些粘附分子中的四个显着减少：sE-选择素（p=0.002），ADAMTS13（p=0.023），sICAM-1（p=0.003），和sVCAM-1(p=0.018)。中性粒细胞数量与sICAM-1、血小板、和sP-选择素，以及白细胞之间，sICAM-1和sVCAM-1。大多数显示出显着相关性的分类单元主要属于梭菌目。具体来说,来自梭菌属，g19，g21和g34组均与HbF水平呈负相关；g19，g21和g24与白细胞呈正相关；g19与中性粒细胞和sVCAM-1呈正相关；g34与E和P选择素呈正相关。Serratia,机会性病原体，与sE-选择素和sICAM-1水平呈正相关。此外,sP-选择素与双歧杆菌呈负相关。该领域的研究可以提高我们的理解，并有助于发现新的预后生物标志物，以确保精确的SCA患者分层并预测严重的并发症。
