Immunoglobulin G1 and immunoglobulin G4 antibodies in multiple sclerosis patients treated with IFNβ interact with the endogenous cytokine and activate complement

SethuS.; GovindappaK.; QuinnP.; WadhwaM.; StebbingsR.; BoggildM.; NaisbittD.; KimberI.; PirmohamedM.; ParkK.; SathishJ.

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Immunoglobulin G1 and immunoglobulin G4 antibodies in multiple sclerosis patients treated with IFNβ interact with the endogenous cytokine and activate complement

机译：接受IFNβ治疗的多发性硬化症患者的免疫球蛋白G1和免疫球蛋白G4抗体与内源性细胞因子相互作用并激活补体

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A subset of patients with relapsing-remitting multiple sclerosis (RRMS) on therapy with interferon beta (IFNβ) develop neutralising anti-drug antibodies (ADA) resulting in reduced, or loss of, therapeutic efficacy. The aims were to characterise the relative contributions of anti-IFNβ antibody isotypes to drug neutralising activity, ability of these antibodies to cross-react with endogenous IFNβ, to form immune complexes and activate complement. IFNβ-specific ADA were measured in plasma from RRMS patients treated with IFNβ1a (Rebif?). Neutralisation of endogenous and therapeutic IFNβ by ADA was determined by IFNβ bioassay. IFNβ-ADA profile was predominantly comprised of IgG1 and IgG4 antibody isotypes. The contribution of IgG4-ADA towards neutralising activity was found to be minimal. Neutralising IFNβ-ADA blocks endogenous IFNβ activity. ADA interaction with therapeutic IFNβ results in immune complex formation and complement activation. In summary, IgG1 and IgG4 IFNβ-ADA have the ability to neutralise therapeutic and endogenous protein and to activate complement.

机译：接受干扰素β（IFNβ）治疗的患有复发缓解型多发性硬化症（RRMS）的患者亚群会产生中和性抗药物抗体（ADA），从而导致疗效降低或丧失。目的是表征抗-IFNβ抗体同种型对药物中和活性的相对贡献，这些抗体与内源性IFNβ交叉反应，形成免疫复合物和激活补体的能力。在用IFNβ1a（Rebif？）治疗的RRMS患者的血浆中测量了IFNβ特异性ADA。通过IFNβ生物测定法确定了ADA对内源性和治疗性IFNβ的中和作用。 IFNβ-ADA谱主要由IgG1和IgG4抗体同种型组成。发现IgG4-ADA对中和活性的贡献是最小的。中和IFNβ-ADA可阻断内源性IFNβ活性。 ADA与治疗性IFNβ的相互作用导致免疫复合物的形成和补体激活。总之，IgG1和IgG4IFNβ-ADA具有中和治疗性和内源性蛋白并激活补体的能力。

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《Clinical immunology: The official journal of the Clinical Immunology Society》 |2013年第2期|共9页
作者
SethuS.; GovindappaK.; QuinnP.; WadhwaM.; StebbingsR.; BoggildM.; NaisbittD.; KimberI.; PirmohamedM.; ParkK.; SathishJ.;
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正文语种 eng
中图分类医学免疫学;
关键词
Anti-drug antibody; Complement; Immunogenicity; Interferon beta; Neutralising antibody; Relapsing-remitting multiple sclerosis;

机译：抗药性抗体;补体;免疫原性;干扰素β;中和抗体;复发型多发性硬化;

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1. Immunoglobulin G1 and immunoglobulin G4 antibodies in multiple sclerosis patients treated with IFNβ interact with the endogenous cytokine and activate complement [J] . SethuS., GovindappaK., QuinnP., Clinical immunology: The official journal of the Clinical Immunology Society . 2013,第2期

机译：接受IFNβ治疗的多发性硬化症患者的免疫球蛋白G1和免疫球蛋白G4抗体与内源性细胞因子相互作用并激活补体
2. Complement activation by polyclonal immunoglobulin G1 and G2 antibodies against Staphylococcus aureus, Haemophilus influenzae type b, and tetanus toxoid. [J] . R G Bredius, P C Driedijk, M F Schouten, Infection and immunity . 1992,第11期

机译：通过针对金黄色葡萄球菌，b型流感嗜血杆菌和破伤风类毒素的多克隆免疫球蛋白G1和G2抗体的补体激活。
3. Further study on the specificity and incidence of neutralizing antibodies to interferon (IFN) in relapsing remitting multiple sclerosis patients treated with IFN beta-1a or IFN beta-1b. [J] . Antonelli G, Simeoni E, Bagnato F, Journal of the Neurological Sciences: Official Bulletin of the World Federation of Neurology . 1999,第2期

机译：干扰素（IFN）的中和性抗体在IFN beta-1a或IFN beta-1b治疗的复发缓解型多发性硬化症患者中的特异性和发生率的进一步研究。
4. The effect of phytosterols on the cytokine release from monocytes from multiple sclerosis patients. [D] . Desai, Forum. 2008

机译：植物甾醇对多发性硬化症患者单核细胞释放细胞因子的影响。
5. Immunoglobulin G1 and immunoglobulin G4 antibodies in multiple sclerosis patients treated with IFNβ interact with the endogenous cytokine and activate complement [O] . Swaminathan Sethu, Karthik Govindappa, Paul Quinn, -1

机译：接受IFNβ治疗的多发性硬化症患者的免疫球蛋白G1和免疫球蛋白G4抗体与内源性细胞因子相互作用并激活补体
6. Immunoglobulin G1 and immunoglobulin G4 antibodies in multiple sclerosis patients treated with IFNβ interact with the endogenous cytokine and activate complement [O] . Sethu, Swaminathan, Govindappa, Karthik, Quinn, Paul, 2013

机译：用IFNβ治疗的多发性硬化患者的免疫球蛋白G1和免疫球蛋白G4抗体与内源性细胞因子相互作用并激活补体

Immunoglobulin G1 and immunoglobulin G4 antibodies in multiple sclerosis patients treated with IFNβ interact with the endogenous cytokine and activate complement

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