Truffot Aurélie, Jouve Thomas, Noble Johan, Bardy Béatrice, Malvezzi Paolo, Rostaing Lionel, Stanke-Labesque Françoise, Gautier-Veyret Elodie
Laboratoire de Pharmacologie, Pharmacogénétique et Toxicologie, CHU Grenoble Alpes, 38043 Grenoble, France.
Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation, CHU Grenoble Alpes, 38043 Grenoble, France.
J Clin Med. 2021 Dec 24;11(1):91. doi: 10.3390/jcm11010091.
The presence of anti-HLA antibodies is an increasing challenge in kidney transplantation. Tocilizumab (TCZ), a monoclonal antibody targeting the interleukin-6 receptor (IL-6R), has been proposed to complement conventional desensitization therapy. We aimed to describe TCZ plasma trough concentrations and their variability and to investigate the link between TCZ concentration and the evolution of anti-HLA antibodies. Sensitized kidney-transplant candidates treated monthly with TCZ (8 mg/kg) for desensitization were retrospectively included. TCZ concentrations were determined by liquid chromatography-tandem mass spectrometry. Seventy-four TCZ concentrations from 10 patients were analyzed. The TCZ trough concentration ranged from <1.0 to 52.5 mg·L, with a median of 25.6 mg·L [25th-75th percentiles: 13.2-35.3 mg·L). The inter- and intra-individual coefficients of variation were 55.0% and 33.0%, respectively. The TCZ trough concentration was not related to IL-6 (rho = -0.46, = 0.792), soluble IL-6R (rho = -0.81, = 0.65) concentrations or reduction of anti-HLA antibodies (mixed-effects model adjusting, effect of TCZ trough concentration: rho = -0.004, = 0.26). The individual median TCZ concentration tended to be associated with the number of antibodies, with an initial MFI > 3000 that dropped to <3000 after TCZ treatment (rho = 0.397, = 0.083). TCZ trough concentrations in kidney-transplant candidates treated for desensitization were highly variable. Further studies on larger cohorts are needed to study the possible link between TCZ concentrations and the reduction of anti-HLA antibodies.
抗人白细胞抗原（HLA）抗体的存在给肾移植带来了越来越大的挑战。托珠单抗（TCZ）是一种靶向白细胞介素-6受体（IL-6R）的单克隆抗体，已被提议用于补充传统的脱敏治疗。我们旨在描述TCZ的血浆谷浓度及其变异性，并研究TCZ浓度与抗HLA抗体演变之间的联系。回顾性纳入了每月接受TCZ（8 mg/kg）脱敏治疗的致敏肾移植候选者。通过液相色谱-串联质谱法测定TCZ浓度。分析了10例患者的74个TCZ浓度。TCZ谷浓度范围为<1.0至52.5 mg·L，中位数为25.6 mg·L[第25-75百分位数：13.2-35.3 mg·L）。个体间和个体内变异系数分别为55.0%和33.0%。TCZ谷浓度与IL-6（rho = -0.46，P = 0.792）、可溶性IL-6R（rho = -0.81，P = 0.65）浓度或抗HLA抗体的减少无关（混合效应模型调整，TCZ谷浓度的效应：rho = -0.004，P = 0.26）。个体TCZ浓度中位数倾向于与抗体数量相关，初始平均荧光强度（MFI）>3000，在TCZ治疗后降至<3000（rho = 0.397，P = 0.083）。接受脱敏治疗的肾移植候选者的TCZ谷浓度高度可变。需要对更大的队列进行进一步研究，以探讨TCZ浓度与抗HLA抗体减少之间的可能联系。
