The use of calgranulin-C (S100A12) and fecal zonulin as possible non-invasive markers in children with inflammatory bowel disease: a clinical study

Eur J Pediatr. 2023 Mar;182(3):1299-1308. doi: 10.1007/s00431-022-04771-7. Epub 2023 Jan 13.

Abstract

Calgranulin-C (S100A12) and zonulin are considered markers of intestinal inflammation. Our aim was to evaluate fecal S100A12 (f-S100A12) and fecal zonulin (f-zonulin) in children with inflammatory bowel disease (IBD), compared to fecal calprotectin (FC) and serum inflammatory markers. We enrolled children with a previous diagnosis of Crohn's disease (CD) and ulcerative colitis (UC). F-S100A12, f-zonulin, and FC were determined by enzyme-linked immunosorbent assay (ELISA). Endoscopic examination was considered in the patients who underwent ileocolonoscopy within 2 weeks from the enrollment. One hundred seventeen children, 39.3% with CD and 60.7% with UC were enrolled. In both CD and UC, there was a significant direct correlation between FC and f-S100A12 levels. In children with CD and UC, both FC and f-S100A12 correlated with markers of serum inflammation. We found difference in FC and f-S100A12 levels between patients in clinical relapse and remission (FC: mean 1027 ± 818 mcg/ml vs 580 ± 695 mcg/ml respectively, p = 0.028; f-S100A12: mean 66.4 ± 48.2 mcg/ml vs 42.7 ± 40 mcg/ml, respectively p = 0.02). Moreover, we found difference in FC between children with endoscopic inflammation and remission (mean 825 ± 779 mcg/ml vs 473.3 ± 492 mcg/ml, respectively p = 0.048), as well as for f-S100A12 (53 ± 43 mcg/ml vs mean 31 ± 33 mcg/ml vs, respectively p = 0.019). No significant results were found for f-zonulin.

Conclusion: Our data suggest that f-S100A12 and FC are both useful non-invasive biomarkers in the management of pediatric IBD in follow up and in monitoring endoscopic and clinical relapse.

What is known: • Fecal calprotectin (FC), fecal S100A12 (f- S100A12), and fecal zonulin represent potential noninvasive markers of gut inflammation. • Since S100A12 is predominantly expressed by granulocytes, high levels of f-S100A12 should be more specific for inflammation than FC.

What is new: • FC and f-S100A12 were correlated to each other and despite the lack of correlation with disease location, they were associated with endoscopic inflammation and clinical relapse in children with IBD. • No significant correlations were found between f-zonulin and the inflammatory parameters.

Keywords: Calgranulin-C; Fecal S100A12; Fecal calprotectin; Fecal zonulin; Inflammatory bowel disease.

MeSH terms

  • Adolescent
  • Biomarkers / analysis
  • Child
  • Child, Preschool
  • Colitis, Ulcerative* / blood
  • Colitis, Ulcerative* / diagnosis
  • Colitis, Ulcerative* / pathology
  • Crohn Disease* / blood
  • Crohn Disease* / diagnosis
  • Crohn Disease* / pathology
  • Endoscopy
  • Feces* / chemistry
  • Haptoglobins* / analysis
  • Humans
  • Inflammation / pathology
  • S100A12 Protein* / analysis

Substances

  • S100A12 Protein
  • zonulin
  • Haptoglobins
  • Biomarkers