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

Sanam Soomro, Suresh Venkateswaran, Kamala Vanarsa, Marwa Kharboutli, Malavika Nidhi, Ramya Susarla, Ting Zhang, Prashanth Sasidharan, Kyung Hyun Lee, Joel Rosh, James Markowitz, Claudia Pedroza, Lee A. Denson, Jeffrey Hyams, Subra Kugathasan () and Chandra Mohan ()
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Sanam Soomro: University of Houston
Suresh Venkateswaran: Emory University School of Medicine and Children Health Care of Atlanta
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 Hyun Lee: Center for Clinical Research and Evidence-based Medicine, McGovern Medical School, UT Health Science Center at Houston
Joel Rosh: Division of Gastroenterology, Hepatology, and Nutrition, Goryeb Children’s Hospital, Atlantic Health
James Markowitz: Division of Gastroenterology, Hepatology, and Nutrition, Cohen Children’s Medical Center Of New York
Claudia Pedroza: Center for Clinical Research and Evidence-based Medicine, McGovern Medical School, UT Health Science Center at Houston
Lee A. Denson: Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine
Jeffrey Hyams: Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children’s Medical Center
Subra Kugathasan: Emory University School of Medicine and Children Health Care of Atlanta
Chandra Mohan: University of Houston

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24235-0

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