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Title: Urine metabolome profiling of immune-mediated inflammatory diseases.
Authors: Alonso, Arnald
Julià, Antonio
Vinaixa, Maria
Domènech, Eugeni
Fernández-Nebro, Antonio
Cañete, Juan D
Ferrándiz, Carlos
Tornero, Jesús
Gisbert, Javier P
Nos, Pilar
Casbas, Ana Gutiérrez
Puig, Lluís
González-Álvaro, Isidoro
Pinto-Tasende, José A
Blanco, Ricardo
Rodríguez, Miguel A
Beltran, Antoni
Correig, Xavier
Marsal, Sara
IMID Consortium
Keywords: Autoimmune diseases;Disease activity;Inflammatory diseases;Metabolomics;Urine biomarkers
metadata.dc.subject.mesh: Arthritis, Rheumatoid
Autoimmune Diseases
Case-Control Studies
Colitis, Ulcerative
Crohn Disease
Lupus Erythematosus, Systemic
Magnetic Resonance Spectroscopy
Issue Date: 8-Sep-2016
Abstract: Immune-mediated inflammatory diseases (IMIDs) are a group of complex and prevalent diseases where disease diagnostic and activity monitoring is highly challenging. The determination of the metabolite profiles of biological samples is becoming a powerful approach to identify new biomarkers of clinical utility. In order to identify new metabolite biomarkers of diagnosis and disease activity, we have performed the first large-scale profiling of the urine metabolome of the six most prevalent IMIDs: rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn's disease, and ulcerative colitis. Using nuclear magnetic resonance, we analyzed the urine metabolome in a discovery cohort of 1210 patients and 100 controls. Within each IMID, two patient subgroups were recruited representing extreme disease activity (very high vs. very low). Metabolite association analysis with disease diagnosis and disease activity was performed using multivariate linear regression in order to control for the effects of clinical, epidemiological, or technical variability. After multiple test correction, the most significant metabolite biomarkers were validated in an independent cohort of 1200 patients and 200 controls. In the discovery cohort, we identified 28 significant associations between urine metabolite levels and disease diagnosis and three significant metabolite associations with disease activity (P FDR  This study shows that urine is a source of biomarkers of clinical utility in IMIDs. We have found that IMIDs show similar metabolic changes, particularly between clinically similar diseases and we have found, for the first time, the presence of hub metabolites. These findings represent an important step in the development of more efficient and less invasive diagnostic and disease monitoring methods in IMIDs.
metadata.dc.identifier.doi: 10.1186/s12916-016-0681-8
Appears in Collections:Producción 2020

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