Moderate performance of serum S100A12, in distinguishing inflammatory bowel disease from irritable bowel syndrome

Abstract

BackgroundS100A12, a calcium-binding proinflammatory protein secreted by granulocytes, has been associated with different diseases of inflammatory origin, including inflammatory bowel disease (IBD). In this study, the utility of serum S100A12, in discriminating IBD from irritable bowel syndrome (IBS), was tested.MethodsS100A12 serum levels were determined in 64 patients with ulcerative colitis (UC), 64 with Crohn's disease (CD) and 73 with IBS, by means of an enzyme-linked immunosorbent assay. S100A12 serum levels were evaluated with respect to the levels of known inflammatory markers and patients' characteristics.ResultsThe median values of serum S100A12 levels were 68.2 ng/mL (range: 43.4-147.4) in UC, 70 ng/mL (41.4-169.8) in CD and 43.4 ng/mL (34.4-74.4) in IBS patients. UC and CD patients had significantly higher serum S100A12 levels compared to IBS patients (P = 0.001 for both comparisons). Moreover, a cut-off for serum S100A12 levels of 54.4 ng/mL could predict both UC and CD with a 66.7% sensitivity and a 64.4% specificity. The area under curve was estimated at 0.67 with a 95% confidence interval of 0.60-0.75 (P < 0.001). Considering standard activity indices, higher serum S100A12 levels in active compared to inactive IBD were observed, although the recorded difference did not reach statistical significance. C-reactive protein (CRP) and serum amyloid A (SAA) levels, showed a statistically significant positive correlation with S100A12 (r = 0.39, P = 0.001 and r = 0.23, P = 0.02 respectively).ConclusionsIncreased levels of circulating S100A12 are found in IBD, compared to IBS. When used to distinguish IBD from IBS adult patients, serum S100A12 levels exhibit moderate performance. On the other hand, serum S100A12 may serve as an inflammatory marker in IBD, since it is well correlated with CRP and SAA.

Biomarkers in inflammatory bowel disease: current practices and recent advances

“…(25) S1000A12 is also detectable in serum, but the fecal assay is more sensitive and specific for IBD. (79)…”

The Involvement of Cholesterol in Sepsis and Tolerance to Lipopolysaccharide Highlighted by the Transcriptome Analysis of Zebrafish (Danio rerio)

“…Although the role of this protein in zebrafish is still unknown, S100 proteins are endogenous activators of innate immune responses in mammals, and some of them have proinflammatory properties and are associated with different inflammatory diseases, such as inflammatory bowel disease. [82][83][84] Several genes involved in the relief of oxidative stress as a compensatory mechanism were up-modulated in tolerized zebrafish as described for mammals 85,86 ; these include glutathione peroxidase 7 (GPX7), which mitigates the organ dysfunction during chronic inflammation, and phosphoenolpyruvate synthase, which is an essential enzyme when pyruvate and lactate are used as a carbon source. The upmodulation in tolerized fish suggests a mechanism for avoiding the excess of lactate and hypoxia that induces the organ failure associated with sepsis.…”

Gastrointestinal toxicity biomarkers

“…This protein activates NF-κB signal transduction and enhances cytokine release (Mendoza and Abreu, 2009). S1000A12 is also detectable in serum, but the fecal assay is more sensitive and specific for IBD (Manolakis et al, 2010). Further work with this biomarker is ongoing.…”