Plasma inflammatory and angiogenic protein profiling of patients with sickle cell disease

In this study, we aimed to explore the inflammatory and angiogenic pathways in sickle cell disease (SCD). We used proximity extension assay technology (Olink) to measure 92 plasma proteins involved in inflammation and angiogenesis. Plasma samples were collected from 57 SCD patients (sickle cell anaemia/HbS-β⁰ thalassaemia-thalassaemia) in steady-state and 13 healthy ethnicity-matched healthy controls (HCs). From 15 patients, paired samples were collected during both steady-state and vaso-occlusive episodes (VOEs) and from 23 SCD patients longitudinal samples were collected before and after treatment with either voxelotor (n = 10), hydroxyurea (n = 8) or allogeneic haematopoietic stem-cell transplantation (n = 5). Fifty plasma proteins were differentially expressed in steady-state SCD patients as compared to HC. These included proteins involved in angiogenesis (i.e. ANGPT1, ANGPT2 and VEGFA), the IL-18 signalling pathway (i.e. IL-6, IL-10, IL-18), T-cell activation (i.e. LAG3, PDCD1) and natural killer (NK)-cell activation (CD244, NCR1, GZMB). While proteins involved in angiogenesis and the IL-18 signalling pathway were further upregulated during VOE, levels of several proteins involved in the IL-18 pathway, T-cell and NK-cell activation and angiogenesis, restored towards levels detected in HCs after curative or disease-modifying treatment. These findings might contribute to a better understanding of SCD pathophysiology and identifying potential new targets for therapeutic interventions.