Treatment of inflammatory bowel disease by chemokine receptor-targeted leukapheresis

详细信息    查看全文

• 作者：Michael Eberhardson ; Per Marits ; Martina Jones ; Petra Jones ; Per Karlen ; Mats Karlsson ; Graham Cotton ; Kerry Woznica ; Beatrice Maltman ; Hans Glise ; Ola Winqvist
• 关键词：Leukapheresis ; Inflammatory bowel disease ; Chemokines ; CCR9 ; CCL25 ; Apheresis
• 刊名：Clinical Immunology
• 出版年：2013
• 出版时间：October, 2013
• 年：2013
• 卷：149
• 期：1
• 页码：73-82
• 全文大小：945 K

文摘

Leukapheresis removes circulating leukocytes en route to the target organ. Hitherto unspecific matrixes have been used to remove leukocytes in inflammatory bowel disease (IBD). This report describes a novel selective leukapheresis column based on chemokine-chemokine receptor interaction. We found an increased expression of the gut homing chemokine receptor CCR9 on CD14⁺ monocytes and on CD3⁺ T lymphocytes from IBD patients. Biologically active CCL25 was coupled to a Sepharose matrix and demonstrated to selectively remove CCR9-expressing cells leaving other cell populations largely unaffected. A patient with active ulcerative colitis, was subjected to CCL25-column leukapheresis. Four days after treatment, he experienced clinical improvement and stable disease improvement ensued. The study illustrates that specific cells can be targeted using high affinity interactions, i.e., CCL25-CCR9 interactions to remove pathogenic gut-homing cells. Leukapheresis using the bCCL25 column should be investigated in a clinical phase I trial of patients with inflammatory bowel disease.