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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

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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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Authors and Affiliations

  1. Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

    Rachele Ciccocioppo, Venerina Imbesi, Elena Betti, Vincenzo Boccaccio, Alessandra Gallia, Giuseppina Cristina Cangemi, Gabriella Carnevale Maffe & Gino Roberto Corazza

  2. International Clinical Research Center, St. Anne’s University Hospital and Masaryk University, Pekarska 53, 656 91, Brno, Czech Republic

    Peter Kruzliak

  3. Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Alessandro Vanoli

  4. Haematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Serena Merante

  5. Immuno-Allergy Laboratory of Paediatrics, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Mara De Amici

  6. Interdepartmental Centre of Research in Molecular Medicine-CIRMC, University of Pavia, Pavia, Italy

    Colomba Falcone

  7. Biometry and Clinical Epidemiology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Catherine Klersy

  8. Department of Internal Medicine, Fondazione IRCCA Policlinico San Matteo, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy

    Rachele Ciccocioppo

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  1. Rachele Ciccocioppo
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  2. Venerina Imbesi
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  3. Elena Betti
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  7. Giuseppina Cristina Cangemi
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  8. Gabriella Carnevale Maffe
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  9. Alessandro Vanoli
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  13. Catherine Klersy
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  14. Gino Roberto Corazza
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Correspondence to Rachele Ciccocioppo or Peter Kruzliak.

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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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