P159. RAGE: a new marker for Crohn's disease severity?
A. Maffioli1, E. Moroni1, V. Imbesi2, R. Ciccocioppo2, P. Danelli1, 1Ospedale L. Sacco, Università degli Studi di Milano, Milano, Italy, 2IRCCS Policlinico San Matteo, Università degli Studi di Pavia, Pavia, Italy
RAGE (Receptor for Advanced Glycation End Products) is an immunoglobulin superfamily cell surface receptor involved in inflammatory responses in various human pathologies. In the study RAGE expression was investigated in intestinal tissue from patients with Crohn's Disease (CD) and from healthy controls and the relationship between RAGE expression and disease behavior, type of surgical intervention and course of disease was analyzed.
20 CD patients and 10 controls (intestinal neoplasia) who underwent surgery were included in the study. During surgery, tissue specimens were obtained from normal and inflamed mucosa in CD patients and only from healthy areas in controls. Formalin-fixed, paraffin-embedded tissue sections underwent pre-treatment with 3 cycles of microwave and then with CAS block solution. The sections were incubated with the polyclonal anti-human RAGE antibody at 1:1000 dilution. RAGE immunoreactivity was analyzed by immunoistochemistry in epitelium and in lamina propria.
RAGE expression was significantly higher both in inflamed and normal areas of CD patients than in controls (p = 0.01). In CD patients there was a significantly increased RAGE expression in inflamed areas compared to normal areas (p = 0.03). RAGE was more expressed in patients with a penetrating disease (p = 0.014) and in patients with multiple disease locations (p = 0.034). RAGE expression was higher in patients who underwent a complex surgical procedure: resection compared to strictureplasty (p = 0.046) and in case of multiple resections or stricturoplasty compared to single surgical procedure (p = 0.019). RAGE was more expressed in patients who had postoperative complications (p = 0.032). RAGE expression was directly related to the number of recurrences observed during the follow-up (p = 0.022), but RAGE wasn't a predictor of early postoperative recurrence.
An increased expression of RAGE in CD compared to control subjects and its overexpression in inflamed areas of CD were of observed. This close correlation of RAGE expression with inflammatory activity suggests that the receptor may play a role in enhancing intestinal inflammation in Crohn's Disease. We found that RAGE expression is correlated with a penetrating phenotype, a severe disease that needs more complex surgery with a higher complications rate and with a higher recurrence rate: RAGE may be a useful marker for identifying patients who are likely to develop severe or complicated disease.