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: Article (Published version)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)