Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy

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dc.citation.volume19
dc.contributor.authorBrachat, Arndt H.
dc.contributor.authorGrom, Alexei A.
dc.contributor.authorWulffraat, Nico
dc.contributor.authorBrunner, Hermine I.
dc.contributor.authorQuartier, Pierre
dc.contributor.authorBrik, Riva
dc.contributor.authorMcCann, Liza
dc.contributor.authorOzdogan, Huri
dc.contributor.authorRutkowska-Sak, Lidia
dc.contributor.authorSchneider, Rayfel
dc.contributor.authorGerloni, Valeria
dc.contributor.authorHarel, Liora
dc.contributor.authorTerreri, Maria [UNIFESP]
dc.contributor.authorHoughton, Kristin
dc.contributor.authorJoos, Rik
dc.contributor.authorKingsbury, Daniel
dc.contributor.authorLopez-Benitez, Jorge M.
dc.contributor.authorBek, Stephan
dc.contributor.authorSchumacher, Martin
dc.contributor.authorValentin, Marie-Anne
dc.contributor.authorGram, Hermann
dc.contributor.authorAbrams, Ken
dc.contributor.authorMartini, Alberto
dc.contributor.authorLovell, Daniel J.
dc.contributor.authorNirmala, Nanguneri R.
dc.contributor.authorRuperto, Nicolino
dc.coverageLondon
dc.date.accessioned2020-07-17T14:03:13Z
dc.date.available2020-07-17T14:03:13Z
dc.date.issued2017
dc.description.abstractBackground: Canakinumab is a human anti-interleukin-1 beta (IL-1 beta) monoclonal antibody neutralizing IL-1 beta-mediated pathways. We sought to characterize the molecular response to canakinumab and evaluate potential markers of response using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA). Methods: Gene expression was measured in patients with febrile SJIA and in matched healthy controls by Affymetrix DNA microarrays. Transcriptional response was assessed by gene expression changes from baseline to day 3 using adapted JIA American College of Rheumatology (aACR) response criteria (50 aACR JIA). Changes in pro-inflammatory cytokines IL-6 and IL-18 were assessed up to day 197. Results: Microarray analysis identified 984 probe sets differentially expressed (>= 2-fold differenceen
dc.description.abstractP < 0.05) in patients versus controls. Over 50% of patients with >= 50 aACR JIA were recognizable by baseline expression values. Analysis of gene expression profiles from patients achieving = 50 aACR JIA response at day 15 identified 102 probe sets differentially expressed upon treatment (>= 2-fold differenceen
dc.description.abstractP < 0.05) on day 3 versus baseline, including IL-1 beta, IL-1 receptors (IL1-R1 and IL1-R2), IL-1 receptor accessory protein (IL1-RAP), and IL-6. The strongest clinical response was observed in patients with higher baseline expression of dysregulated genes and a strong transcriptional response on day 3. IL-6 declined by day 3 (>= 8-fold declineen
dc.description.abstractP < 0.0001) and remained suppressed. IL-18 declined on day 57 (>= 1.5-fold decline, P <= 0.002). Conclusions: Treatment with canakinumab in SJIA patients resulted in downregulation of innate immune response genes and reductions in IL-6 and clinical symptoms. Additional research is needed to investigate potential differences in the disease mechanisms in patients with heterogeneous gene transcription profiles.en
dc.description.affiliationNorvartis Inst Biomed Res, Basel, Switzerland
dc.description.affiliationPRCSG, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA
dc.description.affiliationWilhelmina Childrens Hosp, Dept Pediat Immunol & Rheumatol, Utrecht, Netherlands
dc.description.affiliationUniv Paris 05, Unite Immunol Hematol & Rhumatol Pediat, Hop Necker Enfants Malad, Ctr Reference Natl Arthrit Juveniles,IMAGINE Inst, Paris, France
dc.description.affiliationRambam Med Ctr, Dept Pediat B, Haifa, Israel
dc.description.affiliationAlder Hey Childrens NHS Fdn Trust, Liverpool, Merseyside, England
dc.description.affiliationCerrahpasa Tip Fak, Ic Hastaliklari ABD, Romatol BD, Istanbul, Turkey
dc.description.affiliationInst Rheumatol, Paediat Clin, Warsaw, Poland
dc.description.affiliationHosp Sick Children, Div Rheumatol, Toronto, ON, Canada
dc.description.affiliationIst Gaetano Pini, Div Reumatol, Milan, Italy
dc.description.affiliationSchneider Childrens Med Ctr, Pediat Rheumatol Unit, Petah Tiqwa, Israel
dc.description.affiliationUniv Fed Sao Paulo, Pediat, Sao Paulo, Brazil
dc.description.affiliationBritish Columbia Childrens Hosp, Vancouver, BC, Canada
dc.description.affiliationUniv Ziekenhuis Gent, Ctr Kinderreumatol, Ghent, Belgium
dc.description.affiliationRandall Children’s Hospital at Legacy Emanuel, Portland, OR, USA
dc.description.affiliationFloating Hosp Children, Rheumatol NEMC 286, Boston, MA USA
dc.description.affiliationNovartis Pharmaceut, E Hanover, NJ USA
dc.description.affiliationUniv Genoa, Genoa, Italy
dc.description.affiliationPediat II PRINTO, Ist Giannina Gaslini, Genoa, Italy
dc.description.affiliationNovartis Inst Biomed Res, Cambridge, MA USA
dc.description.affiliationUnifespUniv Fed Sao Paulo, Pediat, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNovartis Pharma
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1186/s13075-016-1212-x
dc.identifier.citationArthritis Research & Therapy. London, v. 19, p. -, 2017.
dc.identifier.doi10.1186/s13075-016-1212-x
dc.identifier.fileWOS000396272700003.pdf
dc.identifier.issn1478-6354
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55236
dc.identifier.wosWOS:000396272700003
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofArthritis Research & Therapy
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectBiomarkersen
dc.subjectCanakinumaben
dc.subjectGene expressionen
dc.subjectInterleukin-1 betaen
dc.subjectJuvenile idiopathic arthritisen
dc.subjectSJIAen
dc.titleEarly changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapyen
dc.typeinfo:eu-repo/semantics/article
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