Down-regulation of Interferon signature in systemic lupus erythematosus patients by active immunization with Interferon alpha-Kinoid extended follow-up

Interferon-alpha Kinoid (IFN-K) is a therapeutic vaccine composed of IFN-alpha2b 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 (see GSE39088). Here, we analyzed extended follow-up data from IFN-K-treated patients, in terms of persistence of neutralizing anti-IFN± Abs, gene expression profiling and safety. Follow-up analyses in six patients confirmed a significant correlation between neutralizing anti-IFNalpha Ab titers and decrease in IFN scores compared to baseline. These analyses also revealed an inhibitory effect of IFN± blockade on the expression of B cell associated transcripts. Extended clinical (SLEDAI, BILAG, Physician Global Assessment) and biological (binding and neutralizing anti-IFNalpha Ab titers, C3 concentrations and anti double-stranded (ds)DNA Ab titers) follow-up data were collected in 6 IFN-K-treated patients. In these patients, whole blood samples were collected in PAXgene Blood RNA tubes (Qiagen) every 6 months after completion of the initial study. RNA was extracted from these samples, and was also re-extracted from baseline (month 0) and day 168 (month 6) PAXgene tubes stored at -80° from the same patients, and from 10 healthy volunteers.