Department of Nephrology, Kasr AlAiny School of Medicine, Cairo University, Cairo, Egypt.
Department of Nephrology and Kidney Transplantation, Misr International Hospital, Cairo, Egypt.
Transplantation. 2022 Feb 1;106(2):369-372. doi: 10.1097/TP.0000000000003686.
Resistance to the action of rituximab (RTX) has been documented in several diseases. More recently, obinutuzumab (OBZ) has shown promise where RTX has failed in oncology and lupus nephritis. Unlike RTX, OBZ is a weak activator of complement, which may avoid the false-positive complement-dependent cytotoxicity (CDC) crossmatch tests after RTX infusions.
The aim of this study was to explore the effect of OBZ on B-cell depletion in kidney-transplant candidates and its impact on crossmatch test results. We included 12 patients, who were either highly sensitized kidney-transplant candidates or kidney-transplant recipients presenting with antibody-mediated rejection. Six received OBZ, and 6 received RTX. CD-19 counts, flow cytometry, and CDC crossmatch tests were run immediately before and at 2 wk after drug infusion.
OBZ reduced CD-19 counts: median reduction was 98%. B-cell CDC crossmatch test results became positive following RTX infusion but were not affected by OBZ infusion.
OBZ effectively depleted B-cell counts in sensitized kidney-transplant candidates and, unlike RTX, had no effect on CDC crossmatch results.
利妥昔单抗(RTX)的耐药性已在多种疾病中得到证实。最近,奥滨尤妥珠单抗(OBZ)在肿瘤学和狼疮性肾炎中显示出 RTX 失败的希望。与 RTX 不同,OBZ 是补体的弱激活剂,这可能避免了 RTX 输注后补体依赖性细胞毒性(CDC)交叉配型试验的假阳性。
本研究旨在探讨 OBZ 对肾移植候选者 B 细胞耗竭的影响及其对交叉配型试验结果的影响。我们纳入了 12 名患者,他们要么是高度致敏的肾移植候选者,要么是出现抗体介导排斥反应的肾移植受者。其中 6 名接受 OBZ 治疗,6 名接受 RTX 治疗。在药物输注前和输注后 2 周,进行 CD-19 计数、流式细胞术和 CDC 交叉配型试验。
OBZ 降低了 CD-19 计数:中位数降低 98%。RTX 输注后 B 细胞 CDC 交叉配型试验结果呈阳性,但 OBZ 输注未受影响。
OBZ 有效耗竭了致敏肾移植候选者的 B 细胞计数,与 RTX 不同,对 CDC 交叉配型试验结果没有影响。