Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon α-kinoid
| Autor: | Géraldine Grouard-Vogel, Olivier Dhellin, Bernard Fanget, Christian Jorgensen, Estibaliz Lazaro, Xavier Mariette, Edwige Haelterman, Pierre Vandepapelière, François Spertini, Bernard Lauwerys, Frédéric Houssiau, Eric Hachulla |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Immunology Down-Regulation Gene Expression Active immunization Severity of Illness Index law.invention Double-Blind Method Rheumatology Randomized controlled trial Downregulation and upregulation law Interferon Interferon α Severity of illness medicine Humans Lupus Erythematosus Systemic Immunology and Allergy Pharmacology (medical) Lupus erythematosus business.industry Vaccination Interferon-alpha Middle Aged medicine.disease Clinical trial Treatment Outcome Hemocyanins Female business medicine.drug |
| Zdroj: | Arthritis & Rheumatism. 65:447-456 |
| ISSN: | 0004-3591 |
| DOI: | 10.1002/art.37785 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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