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P024 Stratification of ulcerative colitis patients according to distinctive tissue cytokine profiles

Butera A.*1, De Nitto D.2, Ciamberlano B.3, Giuliani A.4, Pica R.2, Pronio A.5, Boirivant M.1

1Istituto Superiore di Sanità, Dept Infectious, Parasitic and Immune-mediated Diseases, Roma, Italy 2Sandro Pertini Hospital, IBD, GE Unit, Roma, Italy 3University “Sapienza”, Dept General Surgery, “P. Stefanini”, Rome, Italy 4Istituto Superiore di Sanità, Dept Environment and Health, Rome, Italy 5University “Sapienza”, Dept. General Surgery, “P. Stefanini”, Roma, Italy

Background

A personalized approach to therapy has great promise to improve disease outcomes. Selection of patients as candidates for the early introduction of highly effective therapy can both maximize treatment efficiency and prevent long-term complications. Ulcerative Colitis (UC) has been associated with an atypical Th2 cell response mediated inflammation, but recent findings showed that Th17 response also participates in the inflammatory process. Although some evidences provided a proof-of-concept that IL-13 is an effector cytokine in UC, administration of anti-human IL-13 neutralizing monoclonal antibody, did not significantly improve clinical response vs placebo in UC patients. However, in the same study, the proportion of patients who achieved clinical remission was statistically significantly higher in the anti-IL13 treated group compared with the placebo group, suggesting that UC patients' subgroups might exist. We hypothesize that UC patients might be stratified according to distinctive cytokine profiles

Methods

We analyzed tissue cytokine in endoscopic biopsies of 40 UC outpatients (27 males, 13 females, disease duration 117±95.61 (mean±SD) months; median: 108 (range 0–384) months) undergoing colonoscopy for clinical relapse. At the time of endoscopy patients Mayo endoscopic score was 2.07±0.74 and 2 (1–3); mean±SD and median (range), respectively. We quantified by RT-qPCR TNF-α, IFN-γ, IL-17 and IL-13 and analyzed the results by r square of the k means four cluster solution.

Results

Only IL-13 and IL-17 mRNA tissue content showed discriminatory ability. A subset of patients (17.5%) showed low IL-13 and IL-17 mRNA tissue content. The remaining patients (82.5%) was distributed in two different clusters characterized by high and low IL-13 mRNA expression in the context of high mRNA IL-17 expression. Patients with low IL-17 and IL-13 mRNA expression showed a shorter disease duration and a lower Mayo endoscopic score when compared to patients with high IL-17 mRNA expression. High IL-13 expression was significantly associated (p<0.05 by Fisher's exact test) with extensive colitis.

Conclusion

Data suggest that the majority of UC patients might be classified into two different groups according to the tissue content of IL-13. Disease extension is differently associated with IL-13 mRNA tissue content.

Supported by Grant RF-2011–02350689 by Italian Ministry of Health to MB.