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

Sanam Soomro,Suresh Venkateswaran,Prashanth Sasidharan,Lee A Denson,Malavika Nidhi,James Markowitz,Joel Rosh,Kyung Hyun Lee,Subra Kugathasan,Jeffrey Hyams,Ramya Susarla,Chandra Mohan,Kamala Vanarsa,Marwa Kharboutli,Claudia Pedroza,Ting Zhang

doi:10.1038/s41467-021-24235-0

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.

Highlights

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
We demonstrate that the utility of comprehensive aptamer-based proteomic screens in identifying disease biomarkers for IBD that outperform the current gold standard, fecal calprotectin
For the initial aptamer-based screen of stool proteins, 24 stool samples were interrogated for 1129 proteins, as detailed in the methods section

Summary

Introduction

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. Baseline stool Fibrinogen, MMP12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. 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. This study utilizes a high-throughput aptamer-based targeted proteomic assay to uncover stool biomarkers for pediatric IBD. We demonstrate that the utility of comprehensive aptamer-based proteomic screens in identifying disease biomarkers for IBD that outperform the current gold standard, fecal calprotectin. The current study represents the first use of this aptamer-based screen in stool samples, and in IBD, representing the largest ever targeted stool proteomic study in IBD

Methods

Results

Conclusion