单克隆抗体引起的输注反应（IRs）可能严重甚至致命。我们使用37名刚开始接受单次50mg静脉注射（IV）利妥昔单抗（rituximab）治疗进展性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL）而尚未接受过治疗的患者的临床数据和血样。其中24名患者（65％）在中位数为78分钟（范围为35-128）和利妥昔单抗剂量为32mg（范围为15-50）时发生了IRs。IR的发生风险与患者或CLL特征、CLL计数或CD20水平、血清rituximab或补体浓度无关。35名患者（95％）发生了细胞因子释放反应，血清中≥1种炎症细胞因子的浓度增加了≥4倍。IRs与γ干扰素诱导的细胞因子IP-10、IL-6和IL-8的输注后血清浓度明显升高有关。所有IR患者的IP-10浓度增加了≥4倍，并且在17名患者中超过检测上限（40,000pg/ml，71％）。相反，只有三名没有IR的患者的血清中IP-10浓度增加了≥4倍（最高22,013pg/ml）。我们的数据表明，通过激活清除循环CLL细胞的效应细胞可能会引发细胞因子释放，在那些γ干扰素诱导的细胞因子水平较高的患者中发生IRs。这些新颖的见解可以为未来研究提供信息，以更好地了解和管理IRs，并了解细胞因子在控制对mAb的细胞毒性免疫反应中的作用。版权所有© 2023 Elsevier Ltd.保留所有权利。

Monoclonal antibody induced infusion reactions (IRs) can be serious and even fatal. We used clinical data and blood samples from 37 treatment naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) initiating therapy for progressive disease with a single 50 mg dose of intravenous (IV) rituximab at 25 mg/h. Twenty-four (65 %) patients had IRs at a median of 78 min (range 35-128) and rituximab dose of 32 mg (range 15-50). IR risk did not correlate with patient or CLL characteristics, CLL counts or CD20 levels, or serum rituximab or complement concentrations. Thirty-five (95 %) patients had cytokine release response with a ≥ 4-fold increase in serum concentration of ≥ 1 inflammatory cytokine. IRs were associated with significantly higher post-infusion serum concentrations of gamma interferon induced cytokines IP-10, IL-6 and IL-8. IP-10 concentrations increased ≥ 4-fold in all patients with an IR and were above the upper limit of detection (40,000 pg/ml) in 17 (71 %). In contrast, to only three (23 %) patients without an IR had an ≥ 4-fold increase in serum concentrations of IP-10 (highest 22,013 pg/ml). Our data suggest that cytokine release could be initiated by activation of effector cells responsible for clearance of circulating CLL cells with IRs occurring in those with higher levels of gamma interferon induced cytokines. These novel insights could inform future research to better understand and manage IRs and understand the role of cytokines in the control of cytotoxic immune responses to mAb.Copyright © 2023 Elsevier Ltd. All rights reserved.