Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/2510
Título : Urine metabolome profiling of immune-mediated inflammatory diseases.
Autor : Alonso, Arnald
Julià, Antonio
Vinaixa, Maria
Domènech, Eugeni
Fernández-Nebro, Antonio
Cañete, Juan D
Ferrándiz, Carlos
Tornero, Jesús
Gisbert, Javier P
Nos, Pilar
Gutiérrez Casbas, Ana
Puig, Lluís
González-Álvaro, Isidoro
Pinto-Tasende, José A
Blanco, Ricardo
Rodríguez, Miguel A
Beltran, Antoni
Correig, Xavier
Marsal, Sara
Filiación: [Alonso,A; Julià,A; Marsal,S] Rheumatology Research Group, Vall d’Hebron Hospital Research Institute, Barcelona, Spain. [Vinaixa,M; Rodríguez,MA; Beltran,A; Correig,X] Centre for Omic Sciences, COS-DEEEA-URV-IISPV, Reus, Spain. [Vinaixa,M; Rodríguez,MA; Beltran,A; Correig,X] Metabolomics Platform, CIBERDEM, Reus, Spain. [Domènech,E; Ferrándiz,C] Hospital Universitari Germans Trias i Pujol, Badalona, Spain. [Domènech,E; Gilbert,JP; Nos,P; Gutiérrez Casbas,A] CIBERehd, Madrid, Spain. [Fernández-Nebro,A] UGC Reumatología, Instituto de Investigación Biomédica (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Cañete,JD] Hospital Clínic de Barcelona and IDIBAPS, Barcelona, Spain. [Tornero,J] Hospital Universitario Guadalajara, Guadalajara, Spain. [Gilbert,JP; González-Álvaro,I] Hospital Universitario de la Princesa and IIS-IP, Madrid, Spain. [Nos,P] Hospital la Fe, Valencia, Spain. [Gutiérrez Casbas,A] Hospital General de Alicante, Alicante, Spain. [>Puig,L] Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Pinto-Tasende,JA] Complejo Hospitalario Juan Canalejo, INIBIC, A Coruña, Spain. [Blanco,R] Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Grupo de Investigación: IMID Consortium
Palabras clave : Metabolomics
Urine biomarkers
Disease activity
Autoimmune diseases
Inflammatory diseases
Artritis psoriásica
Artritis reumatoide
Biomarcadores
Ciclo del ácido cítrico
Enfermedad de crohn
Glicina
Humanos
Enfermedades inflamatorias del intestino
Modelos lineales
Lupus eritematoso sistémico
Espectroscopía de resonancia magnética
Metaboloma
Fenilalanina
Psoriasis
Serina
MeSH: Medical Subject Headings::Diseases::Musculoskeletal Diseases::Joint Diseases::Arthritis::Arthritis, Psoriatic
Medical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Arthritis, Rheumatoid
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biomarkers
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Metabolic Networks and Pathways::Citric Acid Cycle
Medical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Crohn Disease
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Glycine
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Statistical::Linear Models
Medical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Lupus Erythematosus, Systemic
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Spectrum Analysis::Magnetic Resonance Spectroscopy
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolome
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Phenylalanine
Medical Subject Headings::Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Skin Diseases, Papulosquamous::Psoriasis
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Serine
Fecha de publicación : 8-Sep-2016
Editorial : Biomed Central
Cita Bibliográfica: Alonso A, Julià A, Vinaixa M, Domènech E, Fernández-Nebro A, Cañete JD, et al. Urine metabolome profiling of immune-mediated inflammatory diseases. BMC Med. 2016; 14(1):133
Abstract: BACKGROUND 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. METHODS 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. RESULTS 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 < 0.05). Using the validation cohort, we validated 26 of the diagnostic associations and all three metabolite associations with disease activity (P FDR < 0.05). Combining all diagnostic biomarkers using multivariate classifiers we obtained a good disease prediction accuracy in all IMIDs and particularly high in inflammatory bowel diseases. Several of the associated metabolites were found to be commonly altered in multiple IMIDs, some of which can be considered as hub biomarkers. The analysis of the metabolic reactions connecting the IMID-associated metabolites showed an over-representation of citric acid cycle, phenylalanine, and glycine-serine metabolism pathways. CONCLUSIONS 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.
Descripción : Journal Article;
URI: http://hdl.handle.net/10668/2510
Versión del editor : http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0681-8#Abs1
DOI: 10.1186/s12916-016-0681-8
ISSN : 1741-7015 (Online)
Appears in Collections:01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga
01- Artículos - Hospital Regional de Málaga

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