Down-regulation of Interferon signature in systemic lupus erythematosus patients by active immunization with Interferon alpha-Kinoid. Homo sapiens

We performed a phase I/II, randomized, double-blind, placebo-controlled dose-escalation study to examine the safety, immunogenicity, and biological effects of active immunization with interferon alpha-Kinoid (IFN-K) in systemic lupus erythematosus (SLE) patients. Women 18-50 years of age with mild to moderate SLE were immunized with three (n=10) or four doses (n=9) of 30, 60, 120, 240 microgram IFN-K or saline. Anti-IFNalpha antibodies were detected in all IFN-K-immunized patients. Transcriptomic analysis separated patients at baseline into type I IFN signature-positive and -negative groups. IFN-K induced higher anti-IFNalpha titers in signature-positive than in signature-negative patients and, in signature-positive patients, reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNalpha antibody titers, and with baseline IFN score. Overall design: IFN-K or placebo was administered at day 0, day 7, day 28 in all patients. Half the subjects received a fourth injection at day 84 (see treatment protocol)

本研究开展了一项I/II期随机双盲安慰剂对照剂量爬坡试验，旨在评估α干扰素类毒素（interferon alpha-Kinoid, IFN-K）主动免疫用于系统性红斑狼疮（systemic lupus erythematosus, SLE）患者的安全性、免疫原性及生物学效应。纳入年龄18~50岁的轻中度系统性红斑狼疮女性受试者，分别接受3剂（n=10）或4剂（n=9）的30、60、120、240微克IFN-K或生理盐水免疫接种。所有接受IFN-K免疫的受试者均检测到抗α干扰素抗体。转录组学分析将基线受试者分为I型干扰素特征（type I IFN signature）阳性与阴性两组。相较于I型干扰素特征阴性受试者，IFN-K在特征阳性受试者中诱导产生了更高滴度的抗α干扰素抗体；且在特征阳性受试者群体内，IFN-K可降低干扰素诱导基因的表达水平。干扰素评分的下降与抗α干扰素抗体滴度及基线干扰素评分均呈显著相关。试验整体设计：所有受试者均于第0天、第7天及第28天接受IFN-K或安慰剂给药；其中半数受试者于第84天追加第四次注射（详见给药方案）