Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy
| Autor: | Brachat A. H., Grom A. A., Wulffraat N., Brunner H. I., Quartier P., Brik R., McCann L., Ozdogan H., Rutkowska-Sak L., Schneider R., Gerloni V., Harel L., Terreri M., Houghton K., Joos R., Kingsbury D., Lopez-Benitez J. M., Bek S., Schumacher M., Valentin M. -A., Gram H., Abrams K., Martini A., Lovell D. J., Nirmala N. R., Ruperto N., Cuttica R., Emminger W., Lauwerys B., Wouters C., Goffin L., Sztajnbok F., Radominski S., Oliveira S., Haddad E., Kone-Paut I., Desjonqueres M., Fischbach M., Thon A., Foell D., Weibarth-Riedel E., Horneff G., Trauzeddel R., Berner R., Kallinich T., Trachana M., Constantin T., Barash J., Berkun Y., Uziel Y., Corona F., Alessio M., Cimaz R., Viola S., Flato B., Ferrandiz M., Calvo I., Anton J., Robledillos J. C., Gamir M. L., Magnusson B., Hofer M., Unsal E., Erguven M., Ozen S., Wilkinson N., Chieng A., Ramanan A., Foster H., Nistala K., Higgins G., Marzan K., Schikler K., Morris P. |
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| Přispěvatelé: | Brachat, A. H., Grom, A. A., Wulffraat, N., Brunner, H. I., Quartier, P., Brik, R., Mccann, L., Ozdogan, H., Rutkowska-Sak, L., Schneider, R., Gerloni, V., Harel, L., Terreri, M., Houghton, K., Joos, R., Kingsbury, D., Lopez-Benitez, J. M., Bek, S., Schumacher, M., Valentin, M. -A., Gram, H., Abrams, K., Martini, A., Lovell, D. J., Nirmala, N. R., Ruperto, N., Cuttica, R., Emminger, W., Lauwerys, B., Wouters, C., Goffin, L., Sztajnbok, F., Radominski, S., Oliveira, S., Haddad, E., Kone-Paut, I., Desjonqueres, M., Fischbach, M., Thon, A., Foell, D., Weibarth-Riedel, E., Horneff, G., Trauzeddel, R., Berner, R., Kallinich, T., Trachana, M., Constantin, T., Barash, J., Berkun, Y., Uziel, Y., Corona, F., Alessio, M., Cimaz, R., Viola, S., Flato, B., Ferrandiz, M., Calvo, I., Anton, J., Robledillos, J. C., Gamir, M. L., Magnusson, B., Hofer, M., Unsal, E., Erguven, M., Ozen, S., Wilkinson, N., Chieng, A., Ramanan, A., Foster, H., Nistala, K., Higgins, G., Marzan, K., Schikler, K., Morris, P. |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine SJIA Juvenile Arthritis 0302 clinical medicine Monoclonal Gene expression Child Oligonucleotide Array Sequence Analysis Immunoassay biology Interleukin-18 Antibodies Monoclonal Interleukin-1β Child Preschool Female Interleukin 18 Biomarkers Canakinumab Juvenile idiopathic arthritis Adolescent Arthritis Juvenile Down-Regulation Gene Expression Profiling Humans Interleukin-6 Transcriptome Young Adult Research Article Human medicine.drug medicine.medical_specialty Antibodies Monoclonal Humanized Antibodies 03 medical and health sciences Juvenile idiopathic arthriti Internal medicine medicine Journal Article Preschool Interleukin 6 030203 arthritis & rheumatology Oligonucleotide Array Sequence Analysi business.industry Microarray analysis techniques Interleukin-1 beta Biomarker medicine.disease Rheumatology Gene expression profiling 030104 developmental biology Immunology biology.protein business |
| Zdroj: | Arthritis Research & Therapy, 19(1). BioMed Central Repositório Institucional da UNIFESP Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP Arthritis Research & Therapy |
| ISSN: | 1478-6354 |
| Popis: | Novartis Pharma 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 P < 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 difference P < 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 decline P < 0.0001) and remained suppressed. IL-18 declined on day 57 (>= 1.5-fold decline, P |
| Databáze: | OpenAIRE |
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