Predicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen

• Type of Material: Article
• Authors: Sanam Soomro, University of Houston; Suresh Venkateswaran, Emory University; Kamala Vanarsa, University of Houston; Marwa Kharboutli, University of Houston; Malavika Nidhi, University of Houston; Ramya Susarla, University of Houston; Ting Zhang, University of Houston; Prashanth Sasidharan, University of Houston; Kyung Hyuun Lee, UT Health Science Center at Houston; Joel Rosh, Goryeb Children’s Hospital, Atlantic Health; James Markowitz, Cohen Childrens Med Ctr New York; Claudia Pedroza, UT Health Science Center at Houston; Lee A Denson, Cincinnati Children’s Hospital Medical Center; Jeffrey Hyams, Connecticut Children’s Medical Center; Subramaniam Kugathasan, Emory University; Chandra Mohan, University of Houston
• Language: English
• Date: 2021-06-28
• Publisher: NATURE RESEARCH
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-021-24235-0
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 12
• Issue: 1
• Start Page: 3989
• End Page: 3989
• Grant/Funding Information: This work was supported by a research initiative grant from the Senior Research Award from Crohn’s and Colitis Foundation, New York, NY, under grant number 568731.; This study was also supported by NIDDK grant numbers DK087696, and 5U01DK095745.
• Keywords: FECAL CALPROTECTIN; CHILDREN; Science & Technology; Science & Technology - Other Topics; CROHNS-DISEASE; Multidisciplinary Sciences; BIOMARKER DISCOVERY; INFLAMMATORY-BOWEL-DISEASE; UTILITY
• Research Categories: Health Sciences, Nutrition; Engineering, Biomedical

Abstract

In the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn’s disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD.