P656 Fcgamma Receptor Type IIIa polymorphisms and their correlation with clinical outcome in patients with inflammatory bowel disease during a long term follow up

Poster presentations compared to ileal biopsies from normal controls (NC).A histopathological score was created based on the degree of active (polymorphonuclear) and chronic (mononuclear) infiltrates (1-normal, 5-massive infiltrate).Gene expression analysis was performed using microarrays, and validated by real-time PCR.Gene ontology and clustering were evaluated using bioinformatic tools.Results: Thirty-six subjects [7 NP, 15 pouchitis (10 CP, 5 CLDP) and 14 NC] were recruited.Significant differences of histopathology scores within the pouch were noticed: median activity scores: 1/5 NP, 2/5 CP, 4/5 CLDP (P = 0.001), median chronicity scores 2/5 NP, 3/5 CP, 3/5 CLDP (P = 0.015).Histopathological differences in the proximal ileum were less pronounced.Nonetheless, significant (fold change 2, corrected P 0.05) molecular alterations were detected in the normal appearing proximal ileum of all pouch groups compared with NC: NP (n = 9), CP (n = 80) and CLDP (n = 230).DUOX2 alteration magnitude in the proximal ileum was highest: an increase of 6.0, 9.8 and 21.7 fold change in NP, CP, CLDP respectively, followed by MMP1 and SLC6A14.Moreover, gene alterations in the proximal ileum overlapped with those observed within the pouch: 76% and 97% overlap in CP and CLDP, respectively.Gene ontology analysis for proximal ileal alterations revealed association with multiple biological processes including active and anion transmembrane transporter activity and metallopeptidase activity.Conclusions: Significant gene expression alterations were detected not only within pouches, but also in the proximal ileum.Alterations in the pouch and the proximal ileum were comparable.These findings may suggest that the inflammatory processes occurring in pouch patients are not limited to the surgically manipulated region (the pouch) but rather extend to the proximal ileum, potentially exposing it to further inflammation.