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

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.

Faecal Myeloperoxidase as a Biomarker of Endoscopic Activity in Inflammatory Bowel Disease

“…This may be due in part to difficulties in extracting myeloperoxidase, which is tightly bound to the solid fraction of stool, and may account for the significant variability in extraction of MPO from faeces ranging from 20% to 100%. 13 , 14 , 31 , 51 Furthermore, the methods used to measure fMPO varied and ranged from radio-immunoassays to ELISAs. 14 , 52 The MPO extraction buffer used in the current study contained 0.2% cetrimonium bromide and resulted in the extraction of 117.5% +/- 33.1% of MPO in spiked stool samples [ Supplementary Figure 2 ].…”

“… 53 , 54 Previous studies investigating fMPO as a biomarker in IBD have also generally been limited to 10–75 study participants, and predominantly included those with UC. 13 , 15 , 16 , 51 , 55 These studies investigated the utility of fMPO to predict disease activity but used a variety of measures to assess this, including symptoms/clinical assessment, alternative biomarkers, endoscopic activity, and histological assessment. 13 , 16 , 51 , 55 Until now, there has been no definitive study that links fMPO to endoscopic findings in both CD and UC using validated endoscopy scoring systems and laboratory methodology in a large IBD cohort and control group.…”

The role of gut microbiome in inflammatory bowel disease diagnosis and prognosis

“…In classifying CD and UC, the model using a set of selected proteins showed good performance with an AUC of 0.9. A recent study 108 also reported that stool proteins identified by an aptamer‐based screen and validated by ELISA could distinguish patients with UC from controls or patients with CD from controls. Some of these proteomic stool biomarkers showed a stronger correlation with the disease activity in patients with UC who were followed up longitudinally.…”

Impact of Obesity on the Course of Management of Inflammatory Bowel Disease—A Review

“…Other observations revealed significantly higher concentrations of resistin in pediatric IBD patients compared to the controls. What is more, a positive association between serum resistin and fecal calprotectin together with both CRP and white blood cell count has been noted as well [ 135 , 136 ].…”