Faecal S100A12 as a non-invasive marker distinguishing inflammatory bowel disease from irritable bowel syndrome

Abstract

Objective: S100A12 is a pro-inflammatory protein that is secreted by granulocytes. S100A12 serum levels increase during inflammatory bowel disease (IBD). We performed the first study analysing faecal S100A12 in adults with signs of intestinal inflammation. Methods: Faecal S100A12 was determined by ELISA in faecal specimens of 171 consecutive patients and 24 healthy controls. Patients either suffered from infectious gastroenteritis confirmed by stool analysis (65 bacterial, 23 viral) or underwent endoscopic and histological investigation (32 with Crohn's disease, 27 with ulcerative colitis, and 24 with irritable bowel syndrome; IBS). Intestinal S100A12 expression was analysed in biopsies obtained from all patients. Faecal calprotectin was used as an additional non-invasive surrogate marker. Results: Faecal S100A12 was significantly higher in patients with active IBD (2.45 ¡ 1.15 mg/kg) compared with healthy controls (0.006 ¡ 0.03 mg/kg; p,0.001) or patients with IBS (0.05 ¡ 0.11 mg/ kg; p,0.001). Faecal S100A12 distinguished active IBD from healthy controls with a sensitivity of 86% and a specificity of 100%. We also found excellent sensitivity of 86% and specificity of 96% for distinguishing IBD from IBS. Faecal S100A12 was also elevated in bacterial enteritis but not in viral gastroenteritis. Faecal S100A12 correlated better with intestinal inflammation than faecal calprotectin or other biomarkers. Conclusions: Faecal S100A12 is a novel non-invasive marker distinguishing IBD from IBS or healthy individuals with a high sensitivity and specificity. Furthermore, S100A12 reflects inflammatory activity of chronic IBD. As a marker for neutrophil activation, faecal S100A12 may significantly improve our arsenal of non-invasive biomarkers of intestinal inflammation.

Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation

“…82 However, both markers show correlation with endoscopic and histological inflammation. 183,184 The reported ranges for sensitivity with S100A12 are 86-97%) and specificity 92-100%. 82,183,184 The cut-off most commonly used was 10 µg/g.…”

“…183,184 The reported ranges for sensitivity with S100A12 are 86-97%) and specificity 92-100%. 82,183,184 The cut-off most commonly used was 10 µg/g. However, it should be noted that, unlike calprotectin, most of the studies performed on S100A12 were in children and on a much smaller data set.…”

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

“…[49][50][51][52] However, most studies found no difference in the faecal levels of calprotectin and lactoferrin between IBS patients and healthy controls. 43,44,49,50,[52][53][54][55][56][57][58][59] Only one publication reported that increased levels of faecal calprotectin were correlated with pain severity; however, this result was observed in children displaying both functional abdominal pain and IBS. 60 Key point: (i) Typically, no changes in the levels of the faecal inflammatory markers calprotectin and lactoferrin are reported in IBS patients.…”

Proinflammatory fecal mRNA and childhood bacterial enteric infections

“…The mRNAs correspond to a panel of pro-inflammatory host proteins (IL-1β, IL-6, IL-8, calprotectin and osteoprotegerin (OPG)), which are found in excess in the stool in infectious or inflammatory diarrhea by EIA, or have been found to be associated with the intestinal immune response to infection. [6][7][8][9][10][11] We also compared the resulting transcript ratios to protein concentrations as determined by EIAs for IL-8, calprotectin and OPG. …”