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> Systemic Inflammation in Preclinical Ulcerative Colitis
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Systemic Inflammation in Preclinical Ulcerative Colitis
Bergemalm D.
;
Andersson E.
;
Hultdin J.
;
Eriksson C.
;
Rush S.T.
;
Kalla R.
;
Adams A.T.
;
Keita Å.V.
;
D''Amato M.
;
Gomollón García, F.
(Universidad de Zaragoza)
;
Jahnsen J.
;
Arnott I.D.
;
Bayes M.
;
Bonfiglio F.
;
Boyapati R.K.
;
Carstens A.
;
Casén C.
;
Ciemniejewska E.
;
Dahl F.A.
;
Detlie T.E.
;
Drummond H.E.
;
Ekeland G.S.
;
Ekman D.
;
Frengen A.B.
;
Gullberg M.
;
Gut I.G.
;
Gut M.
;
Heath S.C.
;
Hjelm F.
;
Hjortswang H.
;
Ho G.-T.
;
Jonkers D.
;
Söderholm J.
;
Kennedy N.A.
;
Lees C.W.
;
Lindahl T.
;
Lindqvist M.
;
Merkel A.
;
Modig E.
;
Moen A.E.F.
;
Nilsen H.
;
Nimmo E.R.
;
Noble C.L.
;
Nordberg N.
;
O''Leary K.R.
;
Ocklind A.
;
Olbjørn C.
;
Pettersson E.
;
Pierik M.
;
Dominique, Ricanek P.
;
Satsangi J.
;
Repsilber D.
;
Karling P.
;
Halfvarson J.
;
IBD Character Consortium
Resumen:
Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins. Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored. Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1ß, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-¿B, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis. Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors. © 2021 The Authors
Idioma:
Inglés
DOI:
10.1053/j.gastro.2021.07.026
Año:
2021
Publicado en:
Gastroenterology
161, 5 (2021), 1526-1539.e9
ISSN:
0016-5085
Factor impacto JCR:
33.883 (2021)
Categ. JCR:
GASTROENTEROLOGY & HEPATOLOGY
rank: 3 / 92 = 0.033
(2021)
- Q1
- T1
Factor impacto CITESCORE:
33.0 -
Medicine
(Q1)
Factor impacto SCIMAGO:
7.689 -
Hepatology
(Q1) -
Gastroenterology
(Q1)
Financiación:
info:eu-repo/grantAgreement/EC/FP7/305676/EU/Inflammatory Bowel Disease CHARACTERization by a multi-modal integrated biomarker study/IBD-CHARACTER
Tipo y forma:
Artículo (Versión definitiva)
Área (Departamento):
Area Medicina
(
Dpto. Medicina, Psiqu. y Derm.
)
Debe reconocer adecuadamente la autoría, proporcionar un enlace a la licencia e indicar si se han realizado cambios. Puede hacerlo de cualquier manera razonable, pero no de una manera que sugiera que tiene el apoyo del licenciador o lo recibe por el uso que hace.
Exportado de SIDERAL (2023-05-18-15:23:21)
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Registro creado el 2022-02-10, última modificación el 2023-05-19
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