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P089. Decrease of peripheral leucocytes BIM protein expression in Crohn's disease

S. Hakim1, M. Fumery1, A. Galmiche2, C. Guignant3, J. Thomas1, F. Brazier1, J.-P. Lemouel1, H. Thiebault1, A. Wacrenier1, E. Nguyen-Khac1, J.-L. Dupas1, 1CHU de Amiens, Gastroenterologie, Amiens, France, 2CHU Amiens, Biochimie, France, 80, Amiens, France, 3CHU Amiens, Immunologie, France, 80, Amiens, France

Background

Crohn's disease (CD) is a chronic inflammatory disease of multifactorial origin. The recruitment of immune cells in the intestinal lamina propria (LP) is involved in chronicity of inflammation. The leukocyte apoptosis play a major role in the physiopathology of inflammatory diseases and cancer. Apoptosis depends on proteins of the BCL-2 family. BIM is a BH3-only protein which has a regulatory role, binding to other members of the BCL-2 family protein, and providing them a pro-apoptotic activity. Its regulation is mainly post-transcriptional. The aim of this study was to evaluate peripheral leucocytes BIM expression in CD patients according to disease activity.

Methods

20 patients with CD and 5 controls were included in the study. Active CD was defined by Harvey–Bradshaw score >3, and C reactive protein >10 mg/L, or endoscopic inflammatory lesions. Expression of BIM and BCL-XL proteins were analyzed by western blots in circulating leukocytes. Characterization of leukocytes was performed by flow cytometry.

Results

There were 13 patients with active CD and 7 patients with inactive disease. The BIM/BCl-XL ratio was decreased in patients with active disease compared to both patients with inactive disease (p = 0.03) and controls (p = 0.014). For disease activity, a BIM/BCL-XL ratio threshold of 350 was associated with a negative predictive value of 86%. BIM/BCL-XL ratio was not associated to disease location or fistulizing phenotype and was not predictive of disease remission over time. No correlation was found between BIM/BCL-XL ratio and CRP or Harvey–Bradshaw score. In flow cytometry analysis, BIM protein was expressed by lymphocytes and monocytes, but not by neutrophils.

Conclusion

The results of this first study of post-transcriptional expression of BIM in leucocytes are in accordance with the possible role of immune cells apoptosis in the pathogenesis of CD. Further studies are necessary to better understand the mechanisms of BIM expression regulation in CD.