Serum immune-activation potency and response to anti-TNF-α therapy in Crohn's disease

AIM: To study whether immune-activation stage in serum of adult Crohn's disease (CD) patients correlates with disease activity and with treatment response to antitumor necrosis factor-alpha (TNF-alpha) therapy. METHODS: Serum samples were obtained from 15 adult CD patients introduced to anti-TNF-alpha therapy. The individual stage of immune activation was studied applying our new in vitro assay, in which target cells (donor derived peripheral blood mononuclear cells) were cultured with patient serum and the T-cell activation induced by the patient serum was studied using a panel of markers for effector [interferon gamma (IFN gamma), interleukin (IL)-5] and regulatory T-cells [forkhead transcription factor 3 (FOXP3) and glucocorticoid-induced tumour necrosis factor receptor (GITR)]. The endoscopic disease activity was assessed with the Crohn's disease endoscopic index of severity (CDEIS) before and 3 mo after therapy with an anti-TNF-alpha agent. RESULTS: Low induction of FOXP3 and GITR in target cells cultured in the presence of patient serum was associated with high disease activity i.e. CDEIS assessed before therapy (r = -0.621, P = 0.013 and r = -0.625, P = 0.013, respectively). FOXP3 expression correlated inversely with pre-treatment erythrocyte sedimentation rate (r = -0.548, P = 0.034). Low serum induced FOXP3 (r = -0.600, P = 0.018) and GITR (r = -0.589, P = 0.021) expression and low IFN gamma secretion from target cells (r = -0.538, P = 0.039) associated with treatment response detected as a decrease in CDEIS. CONCLUSION: The immune-activation potency in the patient serum prior to anti-TNF-alpha therapy reflected intestinal inflammation and the therapeutic response. (C) 2010 Baishideng. All rights reserved.