Professor, Head of the Laboratory of Clinical Immunology; Research Institute of Clinical and Experimental Rheumatology named after A.B. Zborovsky, 76 Zemlyachki St., Volgograd, 400138, Russia.
Leading Researcher; Research Institute of Clinical and Experimental Rheumatology named after A.B. Zborovsky, 76 Zemlyachki St., Volgograd, 400138, Russia.
Sovrem Tekhnologii Med. 2021;12(4):72-75. doi: 10.17691/stm2020.12.4.09. Epub 2020 Aug 27.
was to assess the sorption capacity of Ustekinumab, a drug based on interleukins 12 (IL-12) and 23 (IL-23), when using it with a magnetocontrollable sorbent.
To reduce the concentration of proinflammatory cytokines (IL-12, IL-23), the blood of patients with psoriatic arthritis was passed through magnetocontrollable polyacrylamide granules (MPG) of spherical shape with the particle size of 10-100 μm, obtained by emulsion polymerization. Perfusion was performed through a 10 ml column equipped with an electromagnet, into which MPG with immobilized antibodies to IL-12 and IL-23 was added. Ustekinumab, a commercial drug with concentration of monoclonal antibodies equaling 0.2 mg per 1 ml of saline was used as the source of antibodies to these interleukins. The specific sorption capacity of MPG was determined using a column filled with the granules in a volume of 0.2 ml and inducing their subsequent interaction with 1 ml of IL-12 and IL-23 solutions with increasing concentrations.The heparinized blood of 10 patients with psoriatic arthritis of various degrees of activity, who had no parenteral administration of IL-12/IL-23 inhibitors (Ustekinumab) for 12 months, was subjected to treatment. The blood of 10 healthy donors was used as the control; the perfusion procedure was similar.
Digital parameters were measured for each sample before and after the interaction between the sorbent and blood plasma. There was a significant decrease in cytokines from the baseline - by 99.8% (in donors) and by 99.9% (in patients). When using a carbon sorbent, their concentration decreases by 92.6% from the baseline. As a result of sorption, blood cell counts did not change reliably, which is an additional positive aspect of this procedure.
The maximum possible decrease in the level of cytokines has great practical importance, since they play a leading role in the pathogenesis of psoriatic arthritis. The use of a synthesized Ustekinumab-based sorbent is a highly effective way of removing them simultaneously from blood plasma.
评估乌司奴单抗(一种基于白细胞介素 12(IL-12)和 23(IL-23)的药物)与磁控吸附剂联合使用时的吸附能力。
为了降低促炎细胞因子(IL-12、IL-23)的浓度,将患有银屑病关节炎的患者的血液通过尺寸为 10-100μm 的球形磁控聚丙酰胺颗粒(MPG)进行过滤,MPG 是通过乳液聚合获得的。灌注是通过装有电磁体的 10ml 柱进行的,向其中加入固定有抗 IL-12 和 IL-23 抗体的 MPG。乌司奴单抗是一种含有 0.2mg 单克隆抗体的商业药物,每 1ml 盐水中含有 0.2mg 单克隆抗体,被用作这些白细胞介素的抗体来源。使用填充有 0.2ml 颗粒的柱来确定 MPG 的特异性吸附能力,并通过诱导其随后与浓度不断增加的 1mlIL-12 和 IL-23 溶液相互作用来确定。10 名患有不同活动度银屑病关节炎的患者(12 个月内未接受过 IL-12/IL-23 抑制剂(乌司奴单抗)的静脉注射)的肝素化血液接受了治疗。10 名健康供体的血液被用作对照;灌注程序类似。
在吸附剂与血浆相互作用前后,对每个样本的数字参数进行了测量。与基线相比,细胞因子显著下降-在供体中下降 99.8%,在患者中下降 99.9%。使用碳吸附剂时,细胞因子的浓度从基线下降 92.6%。由于吸附作用,血细胞计数没有可靠地变化,这是该程序的另一个积极方面。
最大程度地降低细胞因子水平具有重要的实际意义,因为它们在银屑病关节炎的发病机制中起主导作用。使用合成的基于乌司奴单抗的吸附剂是同时从血浆中去除它们的一种非常有效的方法。