Manwani Deepa, Chen Grace, Carullo Veronica, Serban Stelian, Olowokure Olugbenga, Jang Jungeun, Huggins Matthew, Cohen Hillel W, Billett Henny, Atweh George F, Frenette Paul S, Shi Patricia A
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York
Am J Hematol. 2015 May;90(5):381-5. doi: 10.1002/ajh.23956. Epub 2015 Apr 1.
Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell-neutrophil interactions in sickle cell mice undergoing vaso-occlusion. In this Phase I clinical trial of sickle cell anemia (SCA) patients admitted with pain crisis, we evaluated the status of adhesion molecules on neutrophils in control and IVIG-treated subjects pre- and post-infusion up to 800 mg/kg, the same dose used in murine studies. Mac-1 function significantly decreased from baseline in the low-dose IVIG (200-400 mg/kg) cohorts. IVIG-related adverse events may have occurred in the high-dose (600-800 mg/kg) cohorts. There were no significant increases in neutrophil and leukocyte counts, suggesting that IVIG may more selectively inhibit Mac-1 function as opposed to neutrophil adhesion. This study provides the first in-human validation of pre-clinical murine studies that IVIG can decrease Mac-1 function.
静脉注射免疫球蛋白（IVIG）可减少镰状细胞病小鼠在血管闭塞过程中中性粒细胞与内皮细胞的黏附以及红细胞与中性粒细胞的相互作用。在这项针对因疼痛危象入院的镰状细胞贫血（SCA）患者的I期临床试验中，我们评估了在输注高达800mg/kg（与小鼠研究中使用的剂量相同）的IVIG前后，对照组和接受IVIG治疗的受试者中性粒细胞上黏附分子的状态。在低剂量IVIG（200 - 400mg/kg）队列中，Mac-1功能较基线水平显著降低。高剂量（600 - 800mg/kg）队列中可能发生了与IVIG相关的不良事件。中性粒细胞和白细胞计数没有显著增加，这表明与中性粒细胞黏附相比，IVIG可能更具选择性地抑制Mac-1功能。这项研究首次在人体中验证了临床前小鼠研究的结果，即IVIG可降低Mac-1功能。
