title: 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.
abstract: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov, clinicaltrials.gov, NCT01058343.
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Pôle de pathologies rhumatismales inflammatoires et systémiques, Université catholique de Louvain.
authors.forename: Julie
authors.initials: J
authors.lastname: Ducreux
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Pôle de pathologies rhumatismales inflammatoires et systémiques, Université catholique de Louvain Département de Rhumatologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Frédéric A
authors.initials: FA
authors.lastname: Houssiau
authors.affiliation: Neovacs, Paris.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vandepapelière
authors.affiliation: Clinical Immunology and Therapeutic of Osteoarticular Diseases Unit, Department of Rheumatology, Hôpital Lapeyronie, Montpellier.
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.affiliation: Department of Internal Medicine, Hôpital de Haut Levêque, CHU Bordeaux, Pessac, France.
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Lazaro
authors.affiliation: Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Spertini
authors.affiliation: Neovacs, Paris.
authors.forename: Fabien
authors.initials: F
authors.lastname: Colaone
authors.affiliation: Neovacs, Paris.
authors.forename: Camille
authors.initials: C
authors.lastname: Roucairol
authors.affiliation: Neovacs, Paris.
authors.forename: Marion
authors.initials: M
authors.lastname: Laborie
authors.affiliation: Neovacs, Paris.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Croughs
authors.affiliation: Neovacs, Paris gvogel@neovacs.com.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Grouard-Vogel
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Pôle de pathologies rhumatismales inflammatoires et systémiques, Université catholique de Louvain Département de Rhumatologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Lauwerys
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D057134:Antibodies, Neutralizing; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins
keywords: B cells; interferon alpha; interferon alpha kinoid; interferon signature; systemic lupus erythematosus