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

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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.

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Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Abbreviations

IBD:

Inflammatory bowel diseases

CD:

Crohn’s disease

UC:

Ulcerative Colitis

FC:

Fecal calprotectin

CRP:

C-reactive protein

ESR:

Erythrocyte sedimentation rate

f-S100A12:

Fecal S100A12

PCDAI:

Pediatric Crohn’s Disease Activity Index

PUCAI:

Pediatric Ulcerative Colitis Activity Index Scores

UCEIS:

Ulcerative Colitis Endoscopic Index of Severity

SES-CD:

Simplified endoscopic score for CD

WBC:

White blood cells

Hb:

Hemoglobin   

Ht:

Hematocrit

PLT:

Platelets

ELISA:

Enzyme-linked immunosorbent assay

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Author information

Authors and Affiliations

  1. Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Sabrina Cenni

  2. Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Marianna Casertano, Marco Trani & Caterina Strisciuglio

  3. Department of Public Health, University of Naples “Federico II”, Naples, Italy

    Daniela Pacella

  4. Department of Translational Medical Science, Section of Pediatrics, University of Naples “Federico II”, Naples, Italy

    Massimo Martinelli, Annamaria Staiano & Erasmo Miele

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  1. Sabrina Cenni
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  8. Caterina Strisciuglio
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Contributions

Sabrina Cenni and Marianna Casertano: conceptualized the study, acquired the data, performed the data analysis, drafted the initial manuscript; Marco Trani: acquired the data; Daniela Pacella: performed the data analysis, drafted the initial manuscript; Massimo Martinelli, Annamaria Staiano, Erasmo Miele, and Caterina Strisciuglio: contributed to the conception of the study, revised the article critically for important intellectual content. All authors approved the final manuscript as submitted.

Corresponding author

Correspondence to Caterina Strisciuglio.

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Ethics approval

The Institutional Review Board of the University of Naples “Federico II” approved the study protocol with the registration number 258/20.

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Informed consent was obtained from the parents of all children, and from children themselves if older than 12 years.

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The authors affirm that human research participants provided informed consent for publication.

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The authors declare no competing interests.

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Cenni, S., Casertano, M., Trani, M. et al. 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 182, 1299–1308 (2023). https://doi.org/10.1007/s00431-022-04771-7

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