Differential expression of adhesion molecules in sickle cell anemia and gut microbiome effect

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.