@article{acbe5c11fb854226affd2fcd6f91c433,
title = "Serum Biomarkers Identify Patients Who Will Develop Inflammatory Bowel Diseases Up to 5 Years Before Diagnosis",
abstract = "Background & Aims: Biomarkers are needed to identify patients at risk for development of inflammatory bowel diseases. We aimed to identify serum biomarkers of Crohn's disease and ulcerative colitis that can be detected and quantified before diagnosis. Methods: We obtained serum samples from patients archived before a diagnosis of Crohn's disease (n = 200) or ulcerative colitis (n = 199), as well as from 200 healthy individuals (controls), collected from 1998 through 2013 as part of the US Defense Medical Surveillance System. We measured levels of antibodies against microbes (anti–Saccharomyces cerevisiae IgA or IgG, anti–Escherichia coli outer membrane porin C, anti-CBir1, anti-flagellin 2, anti-flagellin X, and perinuclear anti-neutrophil cytoplasmic antibodies) and 1129 proteins in each sample. We then used functional principal component analysis to derive the time-varying trajectory for each marker, which then was used in a multivariate model to predict disease status. Predictive performances at different prediagnosis timepoints were evaluated using area under the receiver operating characteristic curves (AUROCs). Biological pathways that were up-regulated in serum from patients with Crohn's disease were identified based on changes in protein abundance at different time periods preceding diagnosis. Results: We identified a panel of 51 protein biomarkers that were predictive of Crohn's disease within 5 years with an AUROC of 0.76 and a diagnosis within 1 year with an AUROC of 0.87. Based on the proteins included in the panel, imminent development of CD was associated with changes in the complement cascade, lysosomes, innate immune response, and glycosaminoglycan metabolism. Serum antibodies and proteins identified patients who received a diagnosis of ulcerative colitis within 5 years with an AUROC of only 0.56 and within 1 year with an AUROC of 0.72. Conclusions: We identified a panel of serum antibodies and proteins that were predictive of patients who will receive a diagnosis of Crohn's disease within 5 years with high accuracy. By contrast we did not identify biomarkers associated with future diagnosis of ulcerative colitis.",
keywords = "ASCA, IBD, pANCA, prognostic",
author = "Joana Torres and Francesca Petralia and Takahiro Sato and Pei Wang and Telesco, {Shannon E.} and Choung, {Rok Seon} and Richard Strauss and Li, {Xiao jun} and Laird, {Renee M.} and Gutierrez, {Ramiro L.} and Porter, {Chad K.} and Scott Plevy and Fred Princen and Murray, {Joseph A.} and Riddle, {Mark S.} and Colombel, {Jean Frederic}",
note = "Funding Information: Conflicts of interest These authors disclose the following: Joana Torres has received speaker fees from Takeda and Janssen. Takahiro Sato, Shannon Telesco, and Richard Strauss are employees of Janssen Research and Development. Xiao-jun Li and Fred Princen are employees of Prometheus. Scott Plevy is employee of Synlogic Therapeutics, past employee of Janssen, and shareholder of Johnson & Johnson. Joseph A. Murray has received research grants from ImmunoGenix, Takeda, Cour, and the National Institutes of Health; received payment for lectures from AbbVie, Amgen, Ferring Pharmaceuticals, Shire, and Takeda; received consulting fees from Amgen, Actobiotics, Bioniz, Celimmune, Eli Lilly Janssen Pharmaceuticals Inova Labs, and Innovate; and royalties from Evelo and Torax Medical. Jean Fr{\'e}d{\'e}ric Colombel reports receiving research grants from AbbVie, Janssen Pharmaceuticals, and Takeda; receiving payment for lectures from AbbVie, Amgen, Allergan Inc, Ferring Pharmaceuticals, Shire, and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Genentech, Janssen Pharmaceuticals, Landos, Ipsen, Medimmune, Merck, Novartis, Pfizer, Shire, Takeda, and TiGenix; and holding stock options in Intestinal Biotech Development and Genfit. A patent application named “A panel of biomarkers for inflammatory bowel disease and uses thereof” has been filed between NRMC, Mount Sinai, Janssen Research and Development, and Prometheus (JBI5154USPSP). The remaining authors disclose no conflicts. Funding Information: Funding Support for this study was provided by Janssen Pharmaceuticals and Prometheus Laboratories under a Cooperative Research and Development Agreement entitled “Antimicrobial antibodies as predictors of inflammatory bowel diseases” (CRADA number NMR-11-3920). Joana Torres received support from the Sandford J. Grossman Charitable Trust . Funding Information: Funding Support for this study was provided by Janssen Pharmaceuticals and Prometheus Laboratories under a Cooperative Research and Development Agreement entitled ?Antimicrobial antibodies as predictors of inflammatory bowel diseases? (CRADA number NMR-11-3920). Joana Torres received support from the Sandford J. Grossman Charitable Trust. Publisher Copyright: {\textcopyright} 2020 AGA Institute Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = jul,
doi = "10.1053/j.gastro.2020.03.007",
language = "English (US)",
volume = "159",
pages = "96--104",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "1",
}