Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da UNIFESP |
| Texto Completo: | https://repositorio.unifesp.br/handle/11600/55236 http://dx.doi.org/10.1186/s13075-016-1212-x |
Resumo: | Background: 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 difference |
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Brachat, Arndt H.Grom, Alexei A.Wulffraat, NicoBrunner, Hermine I.Quartier, PierreBrik, RivaMcCann, LizaOzdogan, HuriRutkowska-Sak, LidiaSchneider, RayfelGerloni, ValeriaHarel, LioraTerreri, Maria [UNIFESP]Houghton, KristinJoos, RikKingsbury, DanielLopez-Benitez, Jorge M.Bek, StephanSchumacher, MartinValentin, Marie-AnneGram, HermannAbrams, KenMartini, AlbertoLovell, Daniel J.Nirmala, Nanguneri R.Ruperto, Nicolino2020-07-17T14:03:13Z2020-07-17T14:03:13Z2017Arthritis Research & Therapy. London, v. 19, p. -, 2017.1478-6354https://repositorio.unifesp.br/handle/11600/55236http://dx.doi.org/10.1186/s13075-016-1212-xWOS000396272700003.pdf10.1186/s13075-016-1212-xWOS:000396272700003Background: 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 differenceP < 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 differenceP < 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 declineP < 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.Novartis PharmaNorvartis Inst Biomed Res, Basel, SwitzerlandPRCSG, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USAWilhelmina Childrens Hosp, Dept Pediat Immunol & Rheumatol, Utrecht, NetherlandsUniv Paris 05, Unite Immunol Hematol & Rhumatol Pediat, Hop Necker Enfants Malad, Ctr Reference Natl Arthrit Juveniles,IMAGINE Inst, Paris, FranceRambam Med Ctr, Dept Pediat B, Haifa, IsraelAlder Hey Childrens NHS Fdn Trust, Liverpool, Merseyside, EnglandCerrahpasa Tip Fak, Ic Hastaliklari ABD, Romatol BD, Istanbul, TurkeyInst Rheumatol, Paediat Clin, Warsaw, PolandHosp Sick Children, Div Rheumatol, Toronto, ON, CanadaIst Gaetano Pini, Div Reumatol, Milan, ItalySchneider Childrens Med Ctr, Pediat Rheumatol Unit, Petah Tiqwa, IsraelUniv Fed Sao Paulo, Pediat, Sao Paulo, BrazilBritish Columbia Childrens Hosp, Vancouver, BC, CanadaUniv Ziekenhuis Gent, Ctr Kinderreumatol, Ghent, BelgiumRandall Children’s Hospital at Legacy Emanuel, Portland, OR, USAFloating Hosp Children, Rheumatol NEMC 286, Boston, MA USANovartis Pharmaceut, E Hanover, NJ USAUniv Genoa, Genoa, ItalyPediat II PRINTO, Ist Giannina Gaslini, Genoa, ItalyNovartis Inst Biomed Res, Cambridge, MA USAUniv Fed Sao Paulo, Pediat, Sao Paulo, BrazilWeb of Science-engBiomed Central LtdArthritis Research & TherapyBiomarkersCanakinumabGene expressionInterleukin-1 betaJuvenile idiopathic arthritisSJIAEarly changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLondon19info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000396272700003.pdfapplication/pdf5011374${dspace.ui.url}/bitstream/11600/55236/1/WOS000396272700003.pdf9dd995cd7d63f8cdfe30ec36ed02f8f3MD51open accessTEXTWOS000396272700003.pdf.txtWOS000396272700003.pdf.txtExtracted texttext/plain48031${dspace.ui.url}/bitstream/11600/55236/2/WOS000396272700003.pdf.txtb98bd898699cd306a0ebcbacfdde93e7MD52open accessTHUMBNAILWOS000396272700003.pdf.jpgWOS000396272700003.pdf.jpgIM Thumbnailimage/jpeg6566${dspace.ui.url}/bitstream/11600/55236/4/WOS000396272700003.pdf.jpgdcb3dc47c2aeee54eb35503d2e5d5c20MD54open access11600/552362022-08-01 04:28:18.086open accessoai:repositorio.unifesp.br:11600/55236Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:19:31.788126Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
| dc.title.en.fl_str_mv |
Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy |
| title |
Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy |
| spellingShingle |
Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy Brachat, Arndt H. Biomarkers Canakinumab Gene expression Interleukin-1 beta Juvenile idiopathic arthritis SJIA |
| title_short |
Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy |
| title_full |
Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy |
| title_fullStr |
Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy |
| title_full_unstemmed |
Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy |
| title_sort |
Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy |
| author |
Brachat, Arndt H. |
| author_facet |
Brachat, Arndt H. Grom, Alexei A. Wulffraat, Nico Brunner, Hermine I. Quartier, Pierre Brik, Riva McCann, Liza Ozdogan, Huri Rutkowska-Sak, Lidia Schneider, Rayfel Gerloni, Valeria Harel, Liora Terreri, Maria [UNIFESP] Houghton, Kristin Joos, Rik Kingsbury, Daniel Lopez-Benitez, Jorge M. Bek, Stephan Schumacher, Martin Valentin, Marie-Anne Gram, Hermann Abrams, Ken Martini, Alberto Lovell, Daniel J. Nirmala, Nanguneri R. Ruperto, Nicolino |
| author_role |
author |
| author2 |
Grom, Alexei A. Wulffraat, Nico Brunner, Hermine I. Quartier, Pierre Brik, Riva McCann, Liza Ozdogan, Huri Rutkowska-Sak, Lidia Schneider, Rayfel Gerloni, Valeria Harel, Liora Terreri, Maria [UNIFESP] Houghton, Kristin Joos, Rik Kingsbury, Daniel Lopez-Benitez, Jorge M. Bek, Stephan Schumacher, Martin Valentin, Marie-Anne Gram, Hermann Abrams, Ken Martini, Alberto Lovell, Daniel J. Nirmala, Nanguneri R. Ruperto, Nicolino |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Brachat, Arndt H. Grom, Alexei A. Wulffraat, Nico Brunner, Hermine I. Quartier, Pierre Brik, Riva McCann, Liza Ozdogan, Huri Rutkowska-Sak, Lidia Schneider, Rayfel Gerloni, Valeria Harel, Liora Terreri, Maria [UNIFESP] Houghton, Kristin Joos, Rik Kingsbury, Daniel Lopez-Benitez, Jorge M. Bek, Stephan Schumacher, Martin Valentin, Marie-Anne Gram, Hermann Abrams, Ken Martini, Alberto Lovell, Daniel J. Nirmala, Nanguneri R. Ruperto, Nicolino |
| dc.subject.eng.fl_str_mv |
Biomarkers Canakinumab Gene expression Interleukin-1 beta Juvenile idiopathic arthritis SJIA |
| topic |
Biomarkers Canakinumab Gene expression Interleukin-1 beta Juvenile idiopathic arthritis SJIA |
| description |
Background: 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 difference |
| publishDate |
2017 |
| dc.date.issued.fl_str_mv |
2017 |
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2020-07-17T14:03:13Z |
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2020-07-17T14:03:13Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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Arthritis Research & Therapy. London, v. 19, p. -, 2017. |
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https://repositorio.unifesp.br/handle/11600/55236 http://dx.doi.org/10.1186/s13075-016-1212-x |
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1478-6354 |
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WOS000396272700003.pdf |
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10.1186/s13075-016-1212-x |
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WOS:000396272700003 |
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Arthritis Research & Therapy. London, v. 19, p. -, 2017. 1478-6354 WOS000396272700003.pdf 10.1186/s13075-016-1212-x WOS:000396272700003 |
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https://repositorio.unifesp.br/handle/11600/55236 http://dx.doi.org/10.1186/s13075-016-1212-x |
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eng |
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eng |
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Arthritis Research & Therapy |
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London |
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Biomed Central Ltd |
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Biomed Central Ltd |
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