000110556 001__ 110556 000110556 005__ 20230519145522.0 000110556 0247_ $$2doi$$a10.1053/j.gastro.2021.07.026 000110556 0248_ $$2sideral$$a127447 000110556 037__ $$aART-2021-127447 000110556 041__ $$aeng 000110556 100__ $$aBergemalm D. 000110556 245__ $$aSystemic Inflammation in Preclinical Ulcerative Colitis 000110556 260__ $$c2021 000110556 5060_ $$aAccess copy available to the general public$$fUnrestricted 000110556 5203_ $$aBackground & 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 000110556 536__ $$9info:eu-repo/grantAgreement/EC/FP7/305676/EU/Inflammatory Bowel Disease CHARACTERization by a multi-modal integrated biomarker study/IBD-CHARACTER 000110556 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000110556 590__ $$a33.883$$b2021 000110556 592__ $$a7.689$$b2021 000110556 594__ $$a33.0$$b2021 000110556 591__ $$aGASTROENTEROLOGY & HEPATOLOGY$$b3 / 92 = 0.033$$c2021$$dQ1$$eT1 000110556 593__ $$aHepatology$$c2021$$dQ1 000110556 593__ $$aGastroenterology$$c2021$$dQ1 000110556 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000110556 700__ $$aAndersson E. 000110556 700__ $$aHultdin J. 000110556 700__ $$aEriksson C. 000110556 700__ $$aRush S.T. 000110556 700__ $$aKalla R. 000110556 700__ $$aAdams A.T. 000110556 700__ $$aKeita Å.V. 000110556 700__ $$aD''Amato M. 000110556 700__ $$0(orcid)0000-0003-0076-3529$$aGomollón García, F.$$uUniversidad de Zaragoza 000110556 700__ $$aJahnsen J. 000110556 700__ $$aArnott I.D. 000110556 700__ $$aBayes M. 000110556 700__ $$aBonfiglio F. 000110556 700__ $$aBoyapati R.K. 000110556 700__ $$aCarstens A. 000110556 700__ $$aCasén C. 000110556 700__ $$aCiemniejewska E. 000110556 700__ $$aDahl F.A. 000110556 700__ $$aDetlie T.E. 000110556 700__ $$aDrummond H.E. 000110556 700__ $$aEkeland G.S. 000110556 700__ $$aEkman D. 000110556 700__ $$aFrengen A.B. 000110556 700__ $$aGullberg M. 000110556 700__ $$aGut I.G. 000110556 700__ $$aGut M. 000110556 700__ $$aHeath S.C. 000110556 700__ $$aHjelm F. 000110556 700__ $$aHjortswang H. 000110556 700__ $$aHo G.-T. 000110556 700__ $$aJonkers D. 000110556 700__ $$aSöderholm J. 000110556 700__ $$aKennedy N.A. 000110556 700__ $$aLees C.W. 000110556 700__ $$aLindahl T. 000110556 700__ $$aLindqvist M. 000110556 700__ $$aMerkel A. 000110556 700__ $$aModig E. 000110556 700__ $$aMoen A.E.F. 000110556 700__ $$aNilsen H. 000110556 700__ $$aNimmo E.R. 000110556 700__ $$aNoble C.L. 000110556 700__ $$aNordberg N. 000110556 700__ $$aO''Leary K.R. 000110556 700__ $$aOcklind A. 000110556 700__ $$aOlbjørn C. 000110556 700__ $$aPettersson E. 000110556 700__ $$aPierik M. 000110556 700__ $$aDominique, Ricanek P. 000110556 700__ $$aSatsangi J. 000110556 700__ $$aRepsilber D. 000110556 700__ $$aKarling P. 000110556 700__ $$aHalfvarson J. 000110556 700__ $$aIBD Character Consortium 000110556 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000110556 773__ $$g161, 5 (2021), 1526-1539.e9$$pGastroenterology$$tGastroenterology$$x0016-5085 000110556 8564_ $$s2887094$$uhttps://zaguan.unizar.es/record/110556/files/texto_completo.pdf$$yVersión publicada 000110556 8564_ $$s2759886$$uhttps://zaguan.unizar.es/record/110556/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000110556 909CO $$ooai:zaguan.unizar.es:110556$$particulos$$pdriver 000110556 951__ $$a2023-05-18-15:23:21 000110556 980__ $$aARTICLE