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P040. Serum proteome profile of Crohn's disease patients treated with infliximab: A pilot study

M. Gazouli1, G.J. Mantzaris2, K. Papamichael2, A. Papadopoulou3, K. Vougas3, N. Anagnou1, G. Tsangaris3

1School of Medicine, University of Athens, Greece, Athens, Greece; 21st Department of Gastroenterology, Evangelismos Hospital, Athens, Greece; 3Proteomics Research Unit, Biomedical Research Foundation of the Academy of Athens, Athens, Greece

Background: Despite intense research there is very limited data on factors predicting the response to infliximab (IFX) of patients with Crohn's disease (CD). This is an important unmet demand because a considerable proportion of patients are primary nonresponders (PNR) to IFX. Recent evidence suggests that proteomic analysis may offer protein biomarkers useful for the diagnosis of CD.

Method: This pilot study aims at analyzing the serum proteome profile of CD patients with different response to IFX therapy in an attempt to identify its usefulness to predict response to IFX. We selected 18 patients (6 females, 12 males; aged 36.92±12.45 ys) who were classified as complete responders (CR, n = 6), partial responers (PR, n = 6), or PNR (n = 6) to IFX induction (5 mg/kg iv at weeks 0, 2, 6) as judged by clinical [Harvey-Bradshaw index (HBI)] and serological criteria (serum CRP) at baseline, before each IFX infusion, and 12 weeks after initiation of IFX, and by endoscopic criteria [assessment of the degree of mucosal healing (MH) 12–20 weeks after initiation of IFX over baseline endoscopy]. CR had normal HBI scores, CRP levels and complete MH; PR had a >50% drop in HBI scores and CRP levels and partial MH (residual ulcers and/or cobblestone vs baseline); PNR showed no change or worsened HBI, CRP, and endoscopy. Serum samples obtained at baseline and at 12 weeks were subjected to proteomic analysis, i.e. two-Dimensional Gel Electrophoresis (2DE); picks shown differentiated expression between groups were selected and further characterized by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS).

Results: Despite the small number of individuals tested, we obtain results suggesting that proteomic markers may help understand response to IFX and define markers for response prediction. IFX markedly changed the serum protein profile of CD patients: PNR and PR but not CR over-expressed the proteins APOA1, APOA4, Alpha-1-antitrypsin, beta-2-glycoprotein, clusterin, C1R, C3, C4, fibrinogen, prothrombin, transthyretin, and VTDB. The protein profile could not differentiate between PNR and PR possibly because of heterogeneity of the small sample size.

Conclusion: Proteomics-based approaches are useful tools for providing global disease information and identifying biomarkers in complex diseases, such as CD. This is the first proteomic study on response to IFX in a Greek CD cohort. Validation studies on a larger cohort of patients are currently in progress.