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

• Published in: Rheumatology Vol. 55; no. 10; pp. 1901 - 1905
• Main Authors: Ducreux, Julie, Houssiau, Frédéric A, Vandepapelière, Pierre, Jorgensen, Christian, Lazaro, Estibaliz, Spertini, François, Colaone, Fabien, Roucairol, Camille, Laborie, Marion, Croughs, Thérèse, Grouard-Vogel, Géraldine, Lauwerys, Bernard R
• Format: Journal Article
• Language: English
• Published: England Oxford University Press (OUP) 01.10.2016; Oxford University Press
• Subjects: Adolescent; Adult; Anti-Inflammatory Agents - administration & dosage; Antibodies, Neutralizing - immunology; B-Lymphocytes - immunology; Basic Science; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Human health and pathology; Humans; Interferon-alpha - administration & dosage; Interferon-alpha - immunology; Life Sciences; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - immunology; Lymphocyte Activation - immunology; Male; Middle Aged; Recombinant Proteins - administration & dosage; Rhumatology and musculoskeletal system; Young Adult; interferon signature; systemic lupus erythematosus; interferon alpha kinoid; B cells; interferon alpha
• ISSN: 1462-0324; 1462-0332; 1460-2172
• DOI: 10.1093/rheumatology/kew262

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. 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. 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. IFN-K induces a polyclonal anti-IFNα response that decreases IFN- and B cell-associated transcripts. ClinicalTrials.gov, clinicaltrials.gov, NCT01058343.