PubMed:34298022 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/34298022","sourcedb":"PubMed","sourceid":"34298022","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/34298022","text":"Systemic Inflammation in Preclinical Ulcerative Colitis.\nBACKGROUND \u0026 AIMS: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.\nMETHODS: 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.\nRESULTS: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P \u003c .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-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, 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.\nCONCLUSIONS: 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.","tracks":[{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":56},"obj":"Sentence"},{"id":"T2","span":{"begin":57,"end":75},"obj":"Sentence"},{"id":"T3","span":{"begin":76,"end":125},"obj":"Sentence"},{"id":"T4","span":{"begin":126,"end":250},"obj":"Sentence"},{"id":"T5","span":{"begin":251,"end":259},"obj":"Sentence"},{"id":"T6","span":{"begin":260,"end":452},"obj":"Sentence"},{"id":"T7","span":{"begin":453,"end":535},"obj":"Sentence"},{"id":"T8","span":{"begin":536,"end":690},"obj":"Sentence"},{"id":"T9","span":{"begin":691,"end":902},"obj":"Sentence"},{"id":"T10","span":{"begin":903,"end":911},"obj":"Sentence"},{"id":"T11","span":{"begin":912,"end":1108},"obj":"Sentence"},{"id":"T12","span":{"begin":1109,"end":1314},"obj":"Sentence"},{"id":"T13","span":{"begin":1315,"end":1405},"obj":"Sentence"},{"id":"T14","span":{"begin":1406,"end":1559},"obj":"Sentence"},{"id":"T15","span":{"begin":1560,"end":1781},"obj":"Sentence"},{"id":"T16","span":{"begin":1782,"end":1794},"obj":"Sentence"},{"id":"T17","span":{"begin":1795,"end":1898},"obj":"Sentence"},{"id":"T18","span":{"begin":1899,"end":2070},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":56},"obj":"Sentence"},{"id":"T2","span":{"begin":57,"end":75},"obj":"Sentence"},{"id":"T3","span":{"begin":76,"end":125},"obj":"Sentence"},{"id":"T4","span":{"begin":126,"end":250},"obj":"Sentence"},{"id":"T5","span":{"begin":251,"end":259},"obj":"Sentence"},{"id":"T6","span":{"begin":260,"end":452},"obj":"Sentence"},{"id":"T7","span":{"begin":453,"end":535},"obj":"Sentence"},{"id":"T8","span":{"begin":536,"end":690},"obj":"Sentence"},{"id":"T9","span":{"begin":691,"end":902},"obj":"Sentence"},{"id":"T10","span":{"begin":903,"end":911},"obj":"Sentence"},{"id":"T11","span":{"begin":912,"end":1108},"obj":"Sentence"},{"id":"T12","span":{"begin":1109,"end":1314},"obj":"Sentence"},{"id":"T13","span":{"begin":1315,"end":1405},"obj":"Sentence"},{"id":"T14","span":{"begin":1406,"end":1559},"obj":"Sentence"},{"id":"T15","span":{"begin":1560,"end":1781},"obj":"Sentence"},{"id":"T16","span":{"begin":1782,"end":1794},"obj":"Sentence"},{"id":"T17","span":{"begin":1795,"end":1898},"obj":"Sentence"},{"id":"T18","span":{"begin":1899,"end":2070},"obj":"Sentence"}],"attributes":[{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"},{"subj":"T8","pred":"source","obj":"Inflammaging"},{"subj":"T9","pred":"source","obj":"Inflammaging"},{"subj":"T10","pred":"source","obj":"Inflammaging"},{"subj":"T11","pred":"source","obj":"Inflammaging"},{"subj":"T12","pred":"source","obj":"Inflammaging"},{"subj":"T13","pred":"source","obj":"Inflammaging"},{"subj":"T14","pred":"source","obj":"Inflammaging"},{"subj":"T15","pred":"source","obj":"Inflammaging"},{"subj":"T16","pred":"source","obj":"Inflammaging"},{"subj":"T17","pred":"source","obj":"Inflammaging"},{"subj":"T18","pred":"source","obj":"Inflammaging"},{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"},{"subj":"T8","pred":"source","obj":"Inflammaging"},{"subj":"T9","pred":"source","obj":"Inflammaging"},{"subj":"T10","pred":"source","obj":"Inflammaging"},{"subj":"T11","pred":"source","obj":"Inflammaging"},{"subj":"T12","pred":"source","obj":"Inflammaging"},{"subj":"T13","pred":"source","obj":"Inflammaging"},{"subj":"T14","pred":"source","obj":"Inflammaging"},{"subj":"T15","pred":"source","obj":"Inflammaging"},{"subj":"T16","pred":"source","obj":"Inflammaging"},{"subj":"T17","pred":"source","obj":"Inflammaging"},{"subj":"T18","pred":"source","obj":"Inflammaging"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Inflammaging","color":"#ec93b6","default":true}]}]}}