title: Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon α-kinoid.
abstract: OBJECTIVE
  We developed interferon-α-kinoid (IFN-K), a drug composed of inactivated IFNα coupled to a carrier protein, keyhole limpet hemocyanin. In human IFNα-transgenic mice, IFN-K induces polyclonal antibodies that neutralize all 13 subtypes of human IFNα. We also previously demonstrated that IFN-K slows disease progression in a mouse model of systemic lupus erythematosus (SLE). This study was undertaken to examine the safety, immunogenicity, and biologic effects of active immunization with IFN-K in patients with SLE.
  
  
  METHODS
  We performed a randomized, double-blind, placebo-controlled, phase I/II dose-escalation study comparing 3 or 4 doses of 30 μg, 60 μg, 120 μg, or 240 μg of IFN-K or placebo in 28 women with mild to moderate SLE.
  
  
  RESULTS
  IFN-K was well tolerated. Two SLE flares were reported as serious adverse events, one in the placebo group and the other in a patient who concomitantly stopped corticosteroids 2 days after the first IFN-K dose, due to mild fever not related to infection. Transcriptome analysis was used to separate patients at baseline into IFN signature-positive and -negative groups, based on the spontaneous expression of IFN-induced genes. IFN-K induced anti-IFNα antibodies in all immunized patients. Notably, significantly higher anti-IFNα titers were found in signature-positive patients than in signature-negative patients. In IFN signature-positive patients, IFN-K significantly reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNα antibody titer. Serum complement C3 levels were significantly increased in patients with high anti-IFNα antibody titers.
  
  
  CONCLUSIONS
  These results show that IFN-K is well tolerated, immunogenic, and significantly improves disease biomarkers in SLE patients, indicating that further studies of its clinical efficacy are warranted.
authors.affiliation: Université Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Lauwerys
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.forename: François
authors.initials: F
authors.lastname: Spertini
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Lazaro
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.forename: Edwige
authors.initials: E
authors.lastname: Haelterman
authors.forename: Géraldine
authors.initials: G
authors.lastname: Grouard-Vogel
authors.forename: Bernard
authors.initials: B
authors.lastname: Fanget
authors.forename: Olivier
authors.initials: O
authors.lastname: Dhellin
authors.forename: Pierre
authors.initials: P
authors.lastname: Vandepapelière
authors.forename: Frédéric A
authors.initials: FA
authors.lastname: Houssiau
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D015870:Gene Expression; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*
chemical_list: D016898:Interferon-alpha; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin