title: Treatment of inflammatory bowel disease by chemokine receptor-targeted leukapheresis.
abstract: 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.
authors.affiliation: Department of Medicine, Section of Gastroenterology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Eberhardson
authors.forename: Per
authors.initials: P
authors.lastname: Marits
authors.forename: Martina
authors.initials: M
authors.lastname: Jones
authors.forename: Petra
authors.initials: P
authors.lastname: Jones
authors.forename: Per
authors.initials: P
authors.lastname: Karlen
authors.forename: Mats
authors.initials: M
authors.lastname: Karlsson
authors.forename: Graham
authors.initials: G
authors.lastname: Cotton
authors.forename: Kerry
authors.initials: K
authors.lastname: Woznica
authors.forename: Beatrice
authors.initials: B
authors.lastname: Maltman
authors.forename: Hans
authors.initials: H
authors.lastname: Glise
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
mesh_terms: D000328:Adult; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D019742:Chemokines, CC / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000628:therapy*; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007937:Leukapheresis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D010865:Pilot Projects; D054388:Receptors, CCR / Q000276:immunology*; D055815:Young Adult
chemical_list: C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; D019742:Chemokines, CC; D016207:Cytokines; D054388:Receptors, CCR
keywords: Apheresis; CCL25; CCR9; Chemokines; Inflammatory bowel disease; Leukapheresis