Urine metabolome profiling of immune-mediated inflammatory diseases
Por:
Alonso, A, Julia, A, Vinaixa, M, Domenech, E, Fernandez-Nebro, A, Canete, J, Ferrandiz, C, Tornero, J, Gisbert, J, Nos, P, Gutierrez Casbas, A, Puig, L, Gonzalez-Alvaro, I, Pinto-Tasende, J, Blanco, R, Rodriguez, M, Beltran, A, Correig, X, Marsal, S and IMID Consortium
Publicada:
8 sep 2016
Categoría:
Medicine (miscellaneous)
Resumen:
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
(PFDR < 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 overrepresentation 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.
Filiaciones:
Alonso, A:
Vall dHebron Hosp, Res Inst, Rheumatol Res Grp, Barcelona, Spain
Julia, A:
Vall dHebron Hosp, Res Inst, Rheumatol Res Grp, Barcelona, Spain
Vinaixa, M:
COS DEEEA URV IISPV, Centre Omic Sci, Reus, Spain
CIBERDEM, Metab Platform, Reus, Spain
Domenech, E:
Hosp Badalona Germans Trias & Pujol, Badalona, Spain
CIBERehd, Madrid, Spain
Fernandez-Nebro, A:
Univ Malaga, Hosp Reg Univ Malaga, Inst Investi Biomed IBIMA, UGC Reumatol, Malaga, Spain
Canete, J:
Hosp Clin Barcelona, Barcelona, Spain
IDIBAPS, Barcelona, Spain
Ferrandiz, C:
Hosp Badalona Germans Trias & Pujol, Badalona, Spain
Tornero, J:
Hosp Univ Guadalajara, Guadalajara, Spain
Gisbert, J:
CIBERehd, Madrid, Spain
Hosp Univ Princesa, Madrid, Spain
IIS IP, Madrid, Spain
Nos, P:
CIBERehd, Madrid, Spain
Hosp La Fe, Valencia, Spain
:
CIBERehd, Madrid, Spain
Hosp Gen Alicante, Alicante, Spain
Puig, L:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Pinto-Tasende, J:
INIBIC, Complejo Hosp Juan Canalejo, La Coruna, Spain
Blanco, R:
Hosp Univ Marques Valdecilla, Santander, Spain
Rodriguez, M:
COS DEEEA URV IISPV, Centre Omic Sci, Reus, Spain
CIBERDEM, Metab Platform, Reus, Spain
Beltran, A:
COS DEEEA URV IISPV, Centre Omic Sci, Reus, Spain
CIBERDEM, Metab Platform, Reus, Spain
Correig, X:
COS DEEEA URV IISPV, Centre Omic Sci, Reus, Spain
CIBERDEM, Metab Platform, Reus, Spain
Marsal, S:
Vall dHebron Hosp, Res Inst, Rheumatol Res Grp, Barcelona, Spain
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