Clinical Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Mar 14, 2008; 14(10): 1521-1527
Published online Mar 14, 2008. doi: 10.3748/wjg.14.1521
Regulatory T cells in patients with inflammatory bowel diseases treated with adacolumn granulocytapheresis
Emilio Cuadrado, Marta Alonso, Maria Dolores de Juan, Pilar Echaniz, Juan Ignacio Arenas
Emilio Cuadrado, Marta Alonso, Maria Dolores de Juan, Pilar Echaniz, Juan Ignacio Arenas, Immunology and Digestive units, Hospital Donostia, Donostia 20014, Spain
Author contributions: Cuadrado E designed research and wrote the paper; Alonso M, de Juan MD, and Echaniz P performed research; Arenas JI did clinical studies.
Correspondence to: Dr. Emilio Cuadrado, Immunology Unit, Hospital Donostia, Pº doctor Begiristain s/n, Donostia 20014, San Sebastian, Spain. emilio.cuadradodelbarrio@osakidetza.net
Telephone: +34-943-007155
Fax: +34-943-007110
Received: October 3, 2007
Revised: January 1, 2008
Published online: March 14, 2008
Abstract

AIM: To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be successful in suppressing inflammatory bowel disease (IBD) in animal models.

METHODS: We report four cases of corticosteroid-dependent ulcerative colitis (UC) and two Crohn’s disease (CD) cases with severe cutaneous lesions who received GMA therapy. The frequency of CD4+ CD25high (Tregs) in peripheral blood was analyzed by flow cytometry and the expression of FoxP3 and TGF beta in purified CD4+ T cells was determined by real time PCR prior to and one month after the last apheresis session, and at the time of endoscopic and clinical assessing.

RESULTS: Increased expression of Fox P3 mRNA was found in all five patients who responded to cytapheresis with remission of clinical symptoms, mucosal inflammation and cutaneous lesions, and an increased frequency of circulating Tregs was found in four patients. These changes were not observed in the patient with UC who did no respond to GMA. Variations in TGF-β (mRNA) did not parallel that of FoxP3 mRNA.

CONCLUSION: The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.

Keywords: Adsorptive leukocytapheresis, Regulatory T cells, Inflammatory bowel diseases, Adacolumn, Granulocyte-monocyte adsorptive apheresis