Azathioprine-Induced Peripheral T Cell Apoptosis And Drug Response In Patients With Crohn’s Disease

Background and Aim: the long time interval for a trial of thioupurine therapy and the potential side effects in spite of the proven efficacy, do not encourage their use as early therapeutic option in Crohn’s Disease (CD). The development of tests predictive of responsiveness represents a major attempt in the clinical management of CD patients. Azathioprine (AZA) is able to induce apoptosis of T cells; therefore we analyzed the “in vitro” thiopurine-induced T cells apoptosis in a group of CD patients with known response to a previous treatment with AZA. Methods: peripheral CD4+ T cells from 16 CD patients were stimulated with antiCD3/CD28 mAbs in the presence or absence of AZA or 6-MP or 6-thioguanine; apoptosis was assessed using Annexin V staining. Results: Apoptosis stimulation index (% of apoptotic cells in the presence of thiopurine / % of apoptotic cells in their absence) was significantly lower in non responder when compared to responder patients (1.46 (0.97-1.8) vs. 2.19 (1.58-2.65) median (range), respectively; p=0.002 by Mann Whitney test). Conclusions: evaluation of apoptosis stimulation index of peripheral CD4+T cell induced by AZA might represent a parameter useful for a proper selection of CD patients candidate to thiopurine treatment.