Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon α kinoid phase I/II study.
Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon α kinoid phase I/II study.
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干扰素α类差异诱导中和抗Interferonα抗体，可降低干扰素诱导的和B细胞激活相关的转录本的表达：分析来自干扰素α激体I/II期研究的扩展后续数据。
DOI：
10.1093/rheumatology/kew262
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发表时间：
2016-10
期刊：
影响因子：
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通讯作者：
Lauwerys BR
中科院分区：
文献类型：
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作者：
Ducreux J;Houssiau FA;Vandepapelière P;Jorgensen C;Lazaro E;Spertini F;Colaone F;Roucairol C;Laborie M;Croughs T;Grouard-Vogel G;Lauwerys BR
Objective. IFN α Kinoid（IFN-K）是由IFNα2b与载体蛋白偶联组成的治疗性疫苗。在I/II期安慰剂对照试验中，我们观察到IFN-κ显著降低SLE患者全血RNA样本中的IFN基因特征。在此，我们分析了IFN-K治疗患者的长期随访数据，以评价中和抗IFN α抗体（Ab）的持续性和基因表达谱。方法.在随访研究中纳入的接受IFN-K治疗的患者中采集血清和全血RNA样本，以测定结合和中和抗IFN α Ab滴度，并进行高通量转录组学研究。结果13种IFNα亚型的中和研究证明了IFN-κ诱导的Ab应答的多克隆性质。6例患者的随访分析证实，与基线相比，中和抗IFN α Ab滴度与IFN评分降低之间存在显著相关性。这些分析还揭示了IFNα阻断对B细胞相关转录物表达的抑制作用。结论. IFN-K诱导多克隆抗IFN α应答，减少IFN-和B细胞相关转录物。试验注册：ClinicalTrials.gov，clinicaltrials.gov，NCT 01058343
Objective. IFN α Kinoid (IFN-K) is a therapeutic vaccine composed of IFNα2b coupled to a carrier protein. In a phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the IFN gene signature in whole blood RNA samples from SLE patients. Here, we analysed extended follow-up data from IFN-K-treated patients, in order to evaluate persistence of neutralizing anti-IFNα Abs antibodies (Abs), and gene expression profiling. Methods. Serum and whole blood RNA samples were obtained in IFN-K-treated patients included in the follow-up study, in order to determine binding and neutralizing anti-IFNα Ab titres, and perform high-throughput transcriptomic studies. Results. Neutralization studies of 13 IFNα subtypes demonstrated the polyclonal nature of the Ab response induced by IFN-K. Follow-up analyses in six patients confirmed a significant correlation between neutralizing anti-IFNα Ab titres and decrease in IFN scores compared to baseline. These analyses also revealed an inhibitory effect of IFNα blockade on the expression of B cell associated transcripts. Conclusions. IFN-K induces a polyclonal anti-IFNα response that decreases IFN- and B cell-associated transcripts. Trial registration: ClinicalTrials.gov, clinicaltrials.gov, NCT01058343