Nazarov V D, Lapin S V, Surkova E A, Makshakov G S, Mazing A V, Evdoshenko E P, Totolian A A
Klin Lab Diagn. 2016 Oct;61(10):710-4.
The human recombinant β-interferon is most frequently applied for treatment of remittent recurrent form of multiple sclerosis using pharmaceuticals. The clinical response to applied therapy is absent in some of patients that can be conditioned by development of antibodies too preparations. Depending on possibility of blocking binding of human recombinant β-interferon with its receptor, all antibodies are divided on binding and neutralizing ones. The purpose of study is to investigate analytical and clinical diagnostic parameters of tests using for detection of different types of antibodies synthesized against human recombinant β-interferon. The study sampling consisted of 33 patients with remittent recurrent form of multiple sclerosis receiving therapy with human recombinant β-interferon and also of 40 donors and 15 patients with multiple sclerosis without therapy with human recombinant β-interferon. The concentration of binding antibodies was measured by enzyme-linked immunosorbent assay. Also immune blotting assay was applied. The titer of neutralizing antibodies was determined using cell line HL-116 sensitive to human recombinant β-interferon. The binding and neutralizing antibodies were not detected in donors and patients without human recombinant β-interferon therapy. The prevalence of binding antibodies to human recombinant β-interferon amounted to 57.6% when analysis of samples using immune blotting assay was used and 60.6% when commercial testing system was applied. The statistical analysis of results demonstrated high convergence and correlation of values of concentrations of binding antibodies obtained using immune blotting assay and enzyme-linked immunosorbent assay (r=0.9159, p<0.0001). The clinically significant titers of neutralizing antibodies were detected in 21.21°% of patients. All patients with clinically significant titer of neutralizing antibodies were positive in relation to binding antibodies measured by immune blotting assay and enzyme-linked immunosorbent assay. The high correlation between values of titers of neutralizing antibodies and concentration of binding antibodies measured by immune blotting assay (r=0.7909, p=0.0055). The application in clinical practice of data concerning presence of binding and neutralizing antibodies to human recombinant β-interferon can input into optimization of therapy with expensive biologic preparations in patients with multiple sclerosis and other autoimmune diseases.
人重组β-干扰素最常用于使用药物治疗缓解复发型多发性硬化症。在一些患者中，对应用疗法没有临床反应，这可能是由于针对制剂产生抗体所致。根据阻断人重组β-干扰素与其受体结合的可能性，所有抗体分为结合性和中和性抗体。本研究的目的是调查用于检测针对人重组β-干扰素合成的不同类型抗体的检测方法的分析和临床诊断参数。研究样本包括33例接受人重组β-干扰素治疗的缓解复发型多发性硬化症患者，以及40名捐赠者和15例未接受人重组β-干扰素治疗的多发性硬化症患者。通过酶联免疫吸附测定法测量结合抗体的浓度。还应用了免疫印迹测定法。使用对人重组β-干扰素敏感的HL-116细胞系测定中和抗体的滴度。在未接受人重组β-干扰素治疗的捐赠者和患者中未检测到结合抗体和中和抗体。当使用免疫印迹测定法分析样本时，与人重组β-干扰素结合的抗体的患病率为57.6%，当应用商业检测系统时为60.6%。结果的统计分析表明，使用免疫印迹测定法和酶联免疫吸附测定法获得的结合抗体浓度值具有高度的一致性和相关性（r=0.9159，p<0.0001）。在21.21%的患者中检测到具有临床意义的中和抗体滴度。所有具有临床意义的中和抗体滴度的患者，通过免疫印迹测定法和酶联免疫吸附测定法测量的结合抗体均为阳性。中和抗体滴度值与通过免疫印迹测定法测量的结合抗体浓度之间具有高度相关性（r=0.7909，p=0.0055）。关于人重组β-干扰素结合抗体和中和抗体存在的数据在临床实践中的应用可以为多发性硬化症和其他自身免疫性疾病患者使用昂贵生物制剂的治疗优化提供参考。
