Division of Hematology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Department of Pathology, Duke University School of Medicine, Durham, North Carolina, USA.
Transfusion. 2024 Sep;64(9):1752-1761. doi: 10.1111/trf.17947. Epub 2024 Jul 9.
Neutrophils in sickle cell disease (SCD) are activated, contributing to disease. Red cell exchange (RCE), with the goal of lowering hemoglobin S (HbS), is an important part of therapy for many SCD patients. Whether RCE impacts neutrophil reactivity is unknown.
To determine the effect of RCE on neutrophil activation, SCD patients undergoing RCE in steady-state were enrolled. Neutrophil degranulation responses were examined before/after RCE. Kinetic studies were completed to determine the duration of the effect of RCE on neutrophil function. Degranulation results were examined in relation to white blood cell count, neutrophil count, and HbS levels. The effect of RCE on RBC phosphatidylserine (PS) exposure was examined as a possible contributor to modulation of neutrophil function by RCE.
Twenty-two patients with SCD, genotype SS, who underwent RCE (average pre-RCE HbS 33 ± 14%) were included for the study. RCE significantly decreased neutrophil degranulation responses. The effect of RCE on neutrophil activation was unrelated to cell count and instead directly correlated with HbS. The effect of RCE on neutrophil activation was sustained over several days post-apheresis. Furthermore, while increased RBC PS exposure results in increased neutrophil degranulation, RCE decreases RBC PS exposure.
To our knowledge, this is the first study demonstrating that RCE significantly decreases neutrophil activation in a sustained HbS-dependent manner. Modulation of PS exposure by RCE may be a contributing mechanism by which RCE modulates neutrophil activation. These studies raise the possibility that modulation of neutrophil activation contributes significantly to the therapeutic effect of RCE.
镰状细胞病（SCD）中的中性粒细胞被激活，导致疾病发生。红细胞交换（RCE）的目的是降低血红蛋白 S（HbS），是许多 SCD 患者治疗的重要组成部分。RCE 是否会影响中性粒细胞反应性尚不清楚。
为了确定 RCE 对中性粒细胞活化的影响，招募了处于稳定状态下正在接受 RCE 的 SCD 患者。在 RCE 前后检查中性粒细胞脱颗粒反应。完成动力学研究以确定 RCE 对中性粒细胞功能的影响持续时间。检查脱颗粒结果与白细胞计数、中性粒细胞计数和 HbS 水平的关系。检查 RCE 对 RBC 磷脂酰丝氨酸（PS）暴露的影响，作为 RCE 调节中性粒细胞功能的可能机制。
研究纳入了 22 名接受 RCE（平均 RCE 前 HbS 为 33±14%）的 SS 基因型 SCD 患者。RCE 显著降低了中性粒细胞脱颗粒反应。RCE 对中性粒细胞活化的影响与细胞计数无关，而是与 HbS 直接相关。RCE 对中性粒细胞活化的影响在血液分离后的几天内持续存在。此外，虽然 RBC PS 暴露增加会导致中性粒细胞脱颗粒增加，但 RCE 会降低 RBC PS 暴露。
据我们所知，这是第一项研究表明，RCE 以持续的 HbS 依赖性方式显著降低中性粒细胞活化。RCE 对 PS 暴露的调节可能是 RCE 调节中性粒细胞活化的一种机制。这些研究提出了这样一种可能性，即中性粒细胞活化的调节可能对 RCE 的治疗效果有重要贡献。
