Abstract
Background
RAGE is a transmembrane receptor expressed on immune and endothelial cells, whose binding with its ligands, the S100 calgranulins, leads to chronic inflammation. Conversely, its soluble form (sRAGE) plays a protective role by acting as a decoy. We carried out a cross-sectional analysis of the sRAGE and S100A12 serum levels in patients with Crohn’s disease (CD) and ulcerative colitis (UC) and searched for a correlation with clinical and biological markers of activity.
Methods
We enrolled 60 CD, 67 UC patients, and 66 controls (all adults). Disease activity was scored through the clinical, endoscopic, and histologic indexes of severity, whilst disease location and behaviour were assessed according to the Montreal classification. In all cases, the levels of serum sRAGE, S100A12, C-reactive protein, and faecal calprotectin were measured.
Results
sRAGE levels were significantly lower in UC, both active and inactive, than in controls and CD (817.35, range 437.3–1449; 1211, range 843.7–1618; 1207.5, range 743.15–1875.75; P < 0.05 for both), and inversely correlated with clinical and endoscopic indexes of activity in both IBD groups (P < 0.05 for all) and with the histologic score in the CD group. Moreover, those CD patients with a penetrating behaviour showed a significant reduction in both sRAGE (P = 0.006) and S100A12 (P = 0.034) as compared to those with an inflammatory/stricturing pattern. Although S100A12 levels were not found up-regulated, a negative correlation appeared evident with the clinical (r = −0.38) and endoscopic (r = −0.32) indexes of activity in UC and CD, respectively.
Conclusion
These data suggest a different role for RAGE in CD and UC, and a potential use of sRAGE as a new biomarker.
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Abbreviations
- CRP:
-
C-reactive protein
- CD:
-
Crohn’s disease
- CDAI:
-
Crohn’s Disease Activity Index
- CDEIS:
-
Crohn’s Disease Endoscopic Severity Index
- ELISA:
-
Enzyme-linked immunoadsorbent assay
- EN-RAGE:
-
Extracellular newly identified RAGE-binding protein
- GHAS:
-
Global Histologic Disease Activity Score
- IBD:
-
Inflammatory bowel disease
- IBS:
-
Irritable bowel syndrome
- RAGE :
-
Receptor for advanced glycation end products
- SCCAI:
-
Simple Clinical Colitis Activity Index
- sRAGE:
-
Soluble receptor for advanced glycation end products
- UC:
-
Ulcerative colitis
- UCEIS:
-
Ulcerative Colitis Endoscopic Index of Severity
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Acknowledgments
The authors are grateful to Ms. Sheila McVeigh for her thorough revision of the English text. This study was funded by following grants: Progetto di Ricerca Corrente (Code 08061307/11) entitled 'Studio della espressione del recettore per i prodotti finali della glicosilazione avanzata (RAGE) nelle malattie infiammatorie croniche intestinali', Progetto di Ricerca Corrente (Code 08063509) 'Istituzione del Registro Italiano Mastocitosi: studio epidemiologico e biologico della mastocitosi, malattia rara e orfana di farmaci'. The funder had no role in the design, analysis, and writing of the study.
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Ciccocioppo, R., Imbesi, V., Betti, E. et al. The Circulating Level of Soluble Receptor for Advanced Glycation End Products Displays Different Patterns in Ulcerative Colitis and Crohn’s Disease: A Cross-Sectional Study. Dig Dis Sci 60, 2327–2337 (2015). https://doi.org/10.1007/s10620-015-3619-7
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DOI: https://doi.org/10.1007/s10620-015-3619-7