Brief Article
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World J Gastroenterol. Dec 14, 2010; 16(46): 5845-5851
Published online Dec 14, 2010. doi: 10.3748/wjg.v16.i46.5845
Serum immune-activation potency and response to anti-TNF-α therapy in Crohn's disease
Hanne Rintamäki, Taina Sipponen, Harri M Salo, Outi Vaarala, Kaija-Leena Kolho
Hanne Rintamäki, Kaija-Leena Kolho, Division of Gastroenterology, Hospital for Children and Adolescents and Helsinki University Central Hospital, University of Helsinki, Helsinki, FIN-00029, Finland
Taina Sipponen, Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, University of Helsinki, Helsinki, FIN-00029, Finland
Harri M Salo, Outi Vaarala, Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, FIN-00300, Finland
Author contributions: Rintamäki H, Kolho KL and Vaarala O designed the research; Rintamäki H and Salo HM performed the research; Rintamäki H, Sipponen T, Salo HM, Vaarala O and Kolho KL analyzed the data; Rintamäki H, Sipponen T, Salo HM, Vaarala O and Kolho KL wrote the paper.
Supported by The Finnish Cultural Foundation, the Finnish Pediatric Research Foundation, the Päivikki and Sakari Sohlberg Foundation, the Helsinki University Central Hospital Grant, the Orion-Farmos Research Foundation, and the Mary and George C Ehrnrooth Foundation
Correspondence to: Dr. Hanne Rintamäki, Division of Gastroenterology, Hospital for Children and Adolescents and Helsinki University Central Hospital, University of Helsinki, Helsinki, FIN-00029, Finland. hanne.rintamaki@helsinki.fi
Telephone: +358-40-8388083 Fax: +358-9-47172599
Received: May 25, 2010
Revised: July 27, 2010
Accepted: August 3, 2010
Published online: December 14, 2010
Abstract

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 anti-tumor necrosis factor-α (TNF-α) therapy.

METHODS: Serum samples were obtained from 15 adult CD patients introduced to anti-TNF-α 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 γ (IFNγ), 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-α 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 IFNγ 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-α therapy reflected intestinal inflammation and the therapeutic response.

Keywords: Crohn’s disease endoscopic index of severity; Forkhead transcription factor 3; Glucocorticoid-induced tumour necrosis factor receptor; Infliximab; Inflammatory bowel disease