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Leukocytapheresis Therapy of Inflammatory Bowel Disease

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Crohn's Disease and Ulcerative Colitis

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Abstract

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD) is a chronic relapsing-remitting immune disorder that afflicts millions of individuals throughout the world with debilitating symptom impairing performance and quality of life. The chronic nature of IBD means that afflicted individuals need life-long medications and this can lead to drug dependency, loss of response together with medication related adverse side effects as additional morbidity factors. In recent years, the efficacy of anti-tumor necrosis factor (TNF)-α antibodies like infliximab in patients with IBD has validated the role of certain cytokines, notably TNF-α in the immunopathogenesis of both UC and CD. However, a major source of inflammatory cytokines are myeloid lineage leukocytes (granulocytes and monocytes), which in patients with IBD are elevated with activation behavior and prolonged survival time. Therefore, myeloid leukocytes appear to be logical target of therapy in IBD patients. Based on this knowledge, therapeutic leukocytapheresis has been introduced as a non-pharmacologic treatment intervention in patients with active IBD. In early days, centrifugation was applied to deplete the myeloid leukocytes, but this has been replaced by direct hemoperfusion systems, the Adacolumn and the Cellsorba filter column. The Adacolumn is filled with cellulose beads as leukocytapheresis carriers that selectively adsorb myeloid leukocytes together with a significant fraction of platelets. In contrast, the Cellsorba filter removes lymphocytes in addition to myeloid cells. The efficacy rate for leukocytapheresis has been variable, from an 80 % to statistically insignificant level depending on patients’ baseline disease severity and other relevant demographic variable. First episode cases together with steroid naïve patients have responded well, while patient with extensive deep mucosal IBD lesions have not responded. However, leukocytapheresis therapy in IBD holds promise, but the full efficacy of this non-drug strategy warrants additional controlled trials in large cohorts of IBD patients.

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References

  1. Allison MC, Dhillon AP, Lewis WG, Pounder RE, editors. Inflammatory bowel disease. London: Mosby; 1998. p. 9–95.

    Google Scholar 

  2. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology. 1998;115:182–205.

    Article  CAS  PubMed  Google Scholar 

  3. Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347:417–29.

    Article  CAS  PubMed  Google Scholar 

  4. Harris ML, Bayless TM. Dietary antigens as aggravating factors in Crohn’s disease. Dig Dis Sci. 1989;34:1613–4.

    Article  CAS  PubMed  Google Scholar 

  5. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361(21):2066–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet. 2012;380(9853):1606–19.

    Article  PubMed  Google Scholar 

  7. Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380(9853):1590–605.

    Article  PubMed  Google Scholar 

  8. Hart AL, Ng SC, Mann E, Al-Hassi HO, Bernardo D, Knight SC. Homing of immune cells: role in homeostasis and intestinal inflammation. Inflamm Bowel Dis. 2010;16(11):1969–77.

    Article  PubMed  Google Scholar 

  9. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Molodecky NA, Panaccione R, Ghosh S, Barkema HW, Kaplan GG. Alberta Inflammatory Bowel Disease Consortium. Challenges associated with identifying the environmental determinants of the inflammatory bowel diseases. Inflamm Bowel Dis. 2011;17(8):1792–9.

    Article  PubMed  Google Scholar 

  11. Wlodarska M, Kostic AD, Xavier RJ. An integrative view of microbiome-host interactions in inflammatory bowel diseases. Cell Host Microbe. 2015;17(5):577–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dalal SR, Chang EB. The microbial basis of inflammatory bowel diseases. J Clin Invest. 2014;124(10):4190–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Shanahan F. Crohn’s disease. Lancet. 2002;359:62–9.

    Article  CAS  PubMed  Google Scholar 

  14. Francescone R, Hou V, Grivennikov SI. Cytokines, IBD, and colitis-associated cancer. Inflamm Bowel Dis. 2015;21(2):409–18.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Brenner D, Blaser H, Mak TW. Regulation of tumor necrosis factor signalling: live or let die. Nat Rev Immunol. 2015;15(6):362–74.

    Article  CAS  PubMed  Google Scholar 

  16. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015;16(5):448–57.

    Article  CAS  PubMed  Google Scholar 

  17. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369(9573):1627–40.

    Article  CAS  PubMed  Google Scholar 

  18. Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014;14(5):329–42.

    Article  CAS  PubMed  Google Scholar 

  19. Schreaiber S, Nikolaus S, Hampe J, Hämling J, Koop I, Groessner B, et al. Tumour necrosis factor alpha and interleukin 1beta in relapse of Crohn’s disease. Lancet. 1999;353:459–61.

    Article  Google Scholar 

  20. Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med. 2000;51:289–98.

    Article  CAS  PubMed  Google Scholar 

  21. Tibble JA, Sigthorsson G, Bridger D, Fagerhol MK, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology. 2000;119:15–22.

    Article  CAS  PubMed  Google Scholar 

  22. Limburg P, David M, Ahlquist A, Sandborn WJ. Faecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhoea referred for colonoscopy. Am J Gastroenterol. 2000;95:2831–7.

    Article  CAS  PubMed  Google Scholar 

  23. Roseth AG, Schmidt PN, Fagerhol MK. Correlation between fecal excretion of Indium-111-labelled granulocytes and calprotectin, a granulocyte marker. Scand J Gastroenterol. 1999;34:50–4.

    Article  CAS  PubMed  Google Scholar 

  24. Ayabe T, Ashida T, Taniguchi M, et al. A pilot study of centrifugal leukocyte apheresis for corticosteroid-resistant active ulcerative colitis. Intern Med. 1997;36:322–6.

    Article  CAS  PubMed  Google Scholar 

  25. Ayabe T, Ashida T, Kohgo Y. Centrifugal leukocyte apheresis for ulcerative colitis. Ther Apher. 1998;2:125–8.

    Article  CAS  PubMed  Google Scholar 

  26. McCarthy DA, Rampton DS, Liu Y-C. Peripheral blood neutrophils in inflammatory bowel disease: morphological evidence of in vivo activation in active disease. Clin Exp Immunol. 1991;86:489–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mahida YR. The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis. 2000;6:21–33.

    Article  CAS  PubMed  Google Scholar 

  28. Hanai H, Watanabe F, Saniabadi A, Matsushita I, Takeuchi K, Iida T. Therapeutic efficacy of granulocyte and monocyte adsorption apheresis in severe active ulcerative colitis. Dig Dis Sci. 2002;47:2349–53.

    Article  PubMed  Google Scholar 

  29. Hanai H, Watanabe F, Takeuchi K, Saniabadi A, Bjarnason I. Leukcocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective uncontrolled pilot study. Clin Gastroenterol Hepatol. 2003;1:28–35.

    Article  PubMed  Google Scholar 

  30. Saniabadi AR, Hanai H, Bjarnason I, Lofberg R. Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial. 2003;7:48–59.

    Article  PubMed  Google Scholar 

  31. Rugtveit J, Brandtzaeg P, Halstensen TS, Fausa O, Scott H. Increased macrophage subsets in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes. Gut. 1994;35:669–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Meuret G, Bitzi A, Hammer B. Macrophage turnover in Crohn’s disease and ulcerative colitis. Gastroenterology. 1978;74:501–3.

    CAS  PubMed  Google Scholar 

  33. Brannigan AE, O’Connell PR, Hurley H. Neutrophil apoptosis is delayed in patients with inflammatory bowel disease. Shock. 2000;13:361–6.

    Article  CAS  PubMed  Google Scholar 

  34. Morse EE, Carbone PP, Freireich EJ, Bronson W, Kliman A. Repeated leukapheresis of patients with chronic myelocytic leukemia. Transfusion. 1966;6:175–82.

    Article  Google Scholar 

  35. Buckner D, Graw Jr RG, Eisel RJ, Henderson ES, Perry S. Leukapheresis by continuous flow centrifugation CFC; in patients with chronic myelocytic leukemia CML. Blood. 1969;33:353–69.

    CAS  PubMed  Google Scholar 

  36. Curtis JE, Hersh EM, Freireich EJ. Leukoapheresis therapy of chronic lymphocytic leukemia. Blood. 1972;39:163–75.

    CAS  PubMed  Google Scholar 

  37. Pearson CM, Paulus HE, Machleder HI. The role of the lymphocyte and its products in the propagation of joint disease. Ann N Y Acad Sci. 1975;256:150–68.

    Article  CAS  PubMed  Google Scholar 

  38. Tenenbaum J, Urowitz MB, Keystone EC, Dwosh IL, Curtis JE. Leukoapheresis in severe rheumatoid arthritis. Ann Rheum Dis. 1979;38:40–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bicks RO, Groshart KW, Chandler RW. The treatment of severe chronically active Crohn’s disease by T8 suppressor cell; lymphapheresis. Gastroenterology. 1985;88:1325.

    Google Scholar 

  40. Bicks RO, Groshart KW, Chandler RW. The treatment of severe chronically active Crohn’s disease by T lymphocyte apheresis. Gastroenterology. 1986;90:A1346.

    Google Scholar 

  41. Bicks RO, Groshart KW, Luther RW. Total parenteral nutrition TPN; plus T-lymphocyte apheresis TLA; in the treatment of severe chronic active Crohn’s disease. Gastroenterology. 1987;94:A34.

    Google Scholar 

  42. Lerebours E, Bussel A, Modigliani R, et al. Treatment of Crohn’s disease by lymphocyte apheresis: a randomized controlled trial. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives. Gastroenterology. 1994;107:357–61.

    Article  CAS  PubMed  Google Scholar 

  43. Kohgo Y, Hibi T, Chiba T, Study group for Alternative Therapies in Ulcerastive Colitis Patients. Leukocyte apheresis using a centrifugal cell separator in refractory ulcerative colitis: a multicenter open label trial. Ther Apher. 2002;6:255–60.

    Article  CAS  PubMed  Google Scholar 

  44. Hiraishi K, Takeda Y, Saniabadi A, et al. Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: an in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis. Ther Apher Dial. 2003;7:334–40.

    Article  PubMed  Google Scholar 

  45. Saniabadi AR, Hanai H, Suzuki Y, Bjarnason I, Lofberg R. Adacolumn for selective leukocytapheresis as a non-pharmacological treatment for patients with disorders of the immune system: an adjunct or an alternative to drug therapy? J Clin Apher. 2005;20:171–84.

    Article  PubMed  Google Scholar 

  46. Hyde GM, Thillainayagam AV, Jewell DP. Intravenous cyclosporin as rescue therapy in severe ulcerative colitis: time for a reappraisal? Eur J Gastroenterol Hepatol. 1998;10:411–3.

    Article  CAS  PubMed  Google Scholar 

  47. Cuadrado E, Alonso M, De Juan MD, Echaniz P, Arenas JI. Regulatory T cells in patients with inflammatory bowel diseases treated with adacolumn granulocytapheresis. World J Gastroenterol. 2008;14:1521–7.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Shimoyama T, Sawada K, Saniabadi A. Safety and efficacy of granulocyte and monocyte apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher. 2001;16:1–9.

    Article  CAS  PubMed  Google Scholar 

  49. Hanauer SB. Can cyclosporine go it alone in severe ulcerative colitis. Curr Gastroenterol Rep. 2001;3:455–6.

    Article  CAS  PubMed  Google Scholar 

  50. Serkova NJ, Christians U, Benet LZ. Biochemical mechanisms of cyclosporine neurotoxicity. Mol Interv. 2004;4:97–107.

    Article  CAS  PubMed  Google Scholar 

  51. Kanke K, Nakano M, Hiraishi H, Terano A. Evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis. Dig Liver Dis. 2004;36:512–8.

    Article  Google Scholar 

  52. Naganuma M, Funakoshi S, Sakuraba A, et al. Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis. Inflamm Bowel Dis. 2004;10:251–7.

    Article  PubMed  Google Scholar 

  53. Yamamoto T, Umegae S, Kitagawa T, Yasuda Y, Yamada Y, Takahashi D. Granulocyte and monocyte adsorptive apheresis in the treatment of active distal ulcerative colitis: a prospective, pilot study. Aliment Pharmacol Ther. 2004;20:783–92.

    Article  CAS  PubMed  Google Scholar 

  54. Premchand P, Takeuchi K, Bjarnason I. Granulocyte, macrophage, monocyte apheresis for refractory ulcerative proctitis. Eur J Gastroenterol Hepatol. 2004;16:943–5.

    Article  PubMed  Google Scholar 

  55. Domenech E, Hinojosa J, Esteve-Comas M, Gassull A, Spanish Group for the Study of Crohn’s Disease and Ulcerative Colitis (GETECCU). Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study. Aliment Pharmacol Ther. 2004;20:1347–52.

    Article  CAS  PubMed  Google Scholar 

  56. Suzuki Y, Yoshimura N, Saniabadi AR, Saito Y. Selective neutrophil and monocyte adsorptive apheresis as a first line treatment for steroid naïve patients with active ulcerative colitis: a prospective uncontrolled study. Dig Dis Sci. 2004;49:565–71.

    Article  CAS  PubMed  Google Scholar 

  57. Cohen RD. Treating ulcerative colitis without medications—“Look Mom, No Drugs!”. Gastroenterology. 2005;128:235–6.

    Article  PubMed  Google Scholar 

  58. Maiden L, Takeuchi K, Bjarnason I, et al. Selective white cell apheresis reduces relapse rates in patients with IBD at significant risk of clinical relapse. Inflamm Bowel Dis. 2008;14:1413–8.

    Article  PubMed  Google Scholar 

  59. Sleasman JW. The association between immunodeficiency and the development of autoimmune disease. Adv Dent Res. 1996;10:57–61.

    Article  CAS  PubMed  Google Scholar 

  60. Matsui T, Nishimura T, Matake H, Ohta T, Sakurai T, Yao T. Granulocytapheresis for Crohn’s disease: a report on seven refractory patients. Am J Gastroenterol. 2003;98:511–2.

    PubMed  Google Scholar 

  61. Fukuda Y, Matsui T, Suzuki Y, Kanke K, Hibi T. Adsorptive granulocyte and monocyte apheresis for refractory Crohn’s disease: an open multicenter prospective study. J Gastroenterol. 2004;39:1158–64.

    Article  PubMed  Google Scholar 

  62. Muratov V, Lundahl J, Ulfgren AK, et al. Downregulation of interferon-g parallels clinical response to selective leukocyte apheresis in patients with inflammatory bowel disease. A 12-month follow-up study. Int J Colorectal Dis. 2006;21(6):493–504.

    Article  CAS  PubMed  Google Scholar 

  63. Hanai H, Watanabe F, Saniabadi A, et al. Correlation of serum soluble TNF-alpha receptors I and II levels with disease activity in patients with ulcerative colitis. Am J Gastroenterol. 2004;99:1532–8.

    Article  CAS  PubMed  Google Scholar 

  64. Mohler KM, Torrance DS, Smith GA, Widmer MB. Soluble tumor necrosis factor TNF; receptors are effective therapeutic agents in lethal endotoximia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol. 1993;151:1548–61.

    CAS  PubMed  Google Scholar 

  65. Kashiwagi N, Hirata I, Kasukawa R. A role for granulocyte and monocyte apheresis in the treatment of rheumatoid arthritis. Ther Apher. 1998;2:134–41.

    Article  CAS  PubMed  Google Scholar 

  66. Ansary MM, Ishihara S, Oka A, Kusunoki R, Oshima N, Yuki T, et al. Apoptotic cells ameliorate chronic intestinal inflammation by enhancing regulatory B-cell function. Inflamm Bowel Dis. 2014;20:2308–20.

    Article  PubMed  Google Scholar 

  67. Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein MR, Isenberg DA, et al. CD19 + CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med. 2013;5:173ra23.

    Article  PubMed  CAS  Google Scholar 

  68. Sono K, Yamada A, Yoshimatsu Y, Takada N, Suzuki Y. Factors associated with the loss of response to infliximab in patients with Crohn’s disease. Cytokine. 2012;59:410–6.

    Article  CAS  PubMed  Google Scholar 

  69. Sawada K, Muto T, Shimoyama T, et al. Multicenter randomized controlled trial for the treatment of ulcerative colitis with a leukocytapheresis colum. Curr Pharm Des. 2003;9:307–21.

    Article  CAS  PubMed  Google Scholar 

  70. Shirokaze J. Leukocytapheresis using a leukocyte removal filter. Ther Apher. 2002;6:261–6.

    Article  CAS  PubMed  Google Scholar 

  71. Sawada K, Ohnishi K, Fukui S. Leukocytapheresis therapy performed with leukocyte removal filter for inflammatory bowel disease. J Gastroenterol. 1995;30:322–9.

    Article  CAS  PubMed  Google Scholar 

  72. Sawada K, Kusugami K, Suzuki Y, et al. Leukocytapheresis in ulcerative colitis: results of a multicenter double-blind prospective case-control study with sham apheresis as placebo treatment. Am J Gastroenterol. 2005;100:1362–9.

    Article  PubMed  Google Scholar 

  73. Sawada K, Egashira A, Ohnishi K, Fukunaga K, Kasuka T, Shimoyama T. Leukocytapheresis LCAP; for management of fulminant ulcerative colitis with toxic megacolon. Dig Dis Sci. 2005;50:767–73.

    Article  CAS  PubMed  Google Scholar 

  74. Sawada K, Muto T, Shimoyama T. Leukocytapheresis with leukocyte removal filter as new therapy for ulcerative colitis. Ther Apher. 1997;1:207–11.

    Article  CAS  PubMed  Google Scholar 

  75. Yamaji K, Yang K, Tsuda H, Hashimoto H. Fluctuations in the peripheral blood leukocyte and platelet counts in leukocytapheresis in healthy volunteers. Ther Apher. 2002;6:402–12.

    Article  PubMed  Google Scholar 

  76. Shibata H, Kuriyama T, Yamawaki N. Cellsorba. Ther Apher Dial. 2003;7:44–7.

    Article  PubMed  Google Scholar 

  77. King C, Ilic A, Koelsch K, Sarvetnick N. Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell. 2004;117:265–77.

    Article  CAS  PubMed  Google Scholar 

  78. Yoshimura N, Tadami T, Kawaguchi T, et al. Processed blood volume impacts clinical efficacy in patients with ulcerative colitis undergoing adsorptive depletion of myeloid lineage leukocytes. J Gastroenterol. 2012;47:49–55.

    Article  PubMed  Google Scholar 

  79. Sakuraba A, Motoya S, Watanabe K, Nishishita M, Kanke K. An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment. Am J Gastroenterol. 2009;104:2990–5.

    Article  PubMed  Google Scholar 

  80. Yamamoto T, Umegae S, Natsumoto K. Daily granulocyte and monocyte adsorptive apheresis in patients with active ulcerative colitis: a prospective safety and feasibility study. J Gastroenterol. 2011;46:1003–9.

    Article  PubMed  Google Scholar 

  81. Sands BE, Sandborn WJ, Feagan B, Adacolumn Study Group, et al. A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for active ulcerative colitis. Gastroenterology. 2008;135:400–9.

    Article  CAS  PubMed  Google Scholar 

  82. Sands BE, Katz S, Wolf DC, et al. A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for moderate to severe Crohn’s disease. Gut. 2013;62:1288–94.

    Article  PubMed  Google Scholar 

  83. Hibi T, Sameshima Y, Sekiguchi Y, et al. Treating ulcerative colitis by Adacolumn therapeutic leucocytapheresis: clinical efficacy and safety based on surveillance of 656 patients in 53 centers in Japan. Dig Liver Dis. 2009;41:570–7.

    Article  CAS  PubMed  Google Scholar 

  84. Yokoyama Y, Matsuoka K, Kobayashi T, et al. A large-scale, prospective, observational study of leukocytapheresis for ulcerative colitis: treatment outcomes of 847 patients in clinical practice. J Crohns Colitis. 2014;8:981–91.

    Article  PubMed  Google Scholar 

  85. Meagher LC, Cousin JM, Seckl JR, Haslett C. Opposing effects of glucocorticoids on the rate of appoptosis in neutrophilic and eosinophilic granulocytes. J Immunol. 1996;156:4422–8.

    CAS  PubMed  Google Scholar 

  86. Cassatella MA. The production of cytokines by polymorphonuclear neutrophils. Immunol Today. 1995;16:21–6.

    Article  CAS  PubMed  Google Scholar 

  87. Nikolaus S, Bauditz J, Gionchetti P. Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin-10 during intestinal inflammation. Gut. 1998;42:470–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Noguchi M, Hiwatashi N, Hayakawa T, Toyota T. Leukocyte removal filter-passed lymphocytes produce large amounts of interleukin-4 in immunotherapy for inflammatory bowel disease: role of bystander suppression. Ther Apher. 1998;2:109–14.

    Article  CAS  PubMed  Google Scholar 

  89. Andoh A, Tsujikawa T, Inatomi O, et al. Leukocytaoheresis therapy modulates circulating T cell subsets in patients with ulcerative colitis. Ther Apher Dial. 2005;9:270–9.

    Article  CAS  PubMed  Google Scholar 

  90. Present DH. How to do without steroids in inflammatory bowel disease. Inflamm Bowel Dis. 2000;6:48–57.

    Article  CAS  PubMed  Google Scholar 

  91. Hanauer SB. Medical therapy of ulcerative colitis. Gastroenterology. 2004;126:1582–92.

    Article  PubMed  Google Scholar 

  92. Bresnihan B, Cunnane G. Infection complications associated with the use of biologic agents. Rheum Dis Clin North Am. 2003;29:185–202.

    Article  PubMed  Google Scholar 

  93. Bromley SK, Thomas SY, Luster AD. Chemokine receptor CCR7 guides T cell exit from peripheral tissues and entry into afferent lymphatics. Nat Immunol. 2005;6:895–901.

    Article  CAS  PubMed  Google Scholar 

  94. Egan LJ, Sandborn WJ. Advances in the treatment of Crohn’s disease. Gastroenterology. 2004;126:1574–81.

    Article  PubMed  Google Scholar 

  95. Shand A, Forbes A. Potential therapeutic role for cytokine or adhesion molecule manipulation in Crohn’s disease: in the shadow of infliximab? Int J Colorectal Dis. 2003;18:1–11.

    Article  PubMed  Google Scholar 

  96. Campbell DJ, Debes GF, Johnston B, Wilson E, Butcher EC. Targeting T cell responses by selective chemokine receptor expression. Semin Immunol. 2003;15:277–86.

    Article  CAS  PubMed  Google Scholar 

  97. Mackay CR, Marston WL, Dudler L. Naïve and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med. 1990;171:801–17.

    Article  CAS  PubMed  Google Scholar 

  98. Olszewski WL. The lymphatic system in body homeostasis: physiological conditions. Lymphat Res Biol. 2003;1:11–21.

    Article  PubMed  Google Scholar 

  99. Debes GF, Arnold CN, Young AJ, et al. Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues. Nat Immunol. 2005;6:889–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Klonowski KD. Dynamics of blood-borne CD8 memory T cell migration in vivo. Immunity. 2004;20:551–62.

    Article  CAS  PubMed  Google Scholar 

  101. Lee A, Whyte M, Haslett C. Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. J Leukoc Biol. 1993;54:283–8.

    CAS  PubMed  Google Scholar 

  102. Suzuki Y, Yoshimura N, Fukuda K, Shirai K, Saito Y, Saniabadi AR. A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis. Dig Dis Sci. 2006;51:2031–8.

    Article  PubMed  Google Scholar 

  103. Study for the treatment of Crohn’s disease with adacolumn. post-hoc: clinical response in subjects with a CDAI score greater than 300. https://clinicaltrials.gov/ct2/home. Accessed June 2015.

  104. Saniabadi AR, Tanaka T, Ohmori T, et al. Treating inflammatory bowel disease by adsorptive leucocytapheresis: a desire to treat without drugs. World J Gastroenterol. 2014;20:9699–715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Hanai H, Takeuchi K, Iida T, et al. Relationship between fecal calprotectin, intestinal inflammation, and peripheral blood neutrophils in patients with active ulcerative colitis. Dig Dis Sci. 2004;49:1438–43.

    Article  PubMed  Google Scholar 

  106. Tanaka T, Okanobu H, Yoshimi S, et al. In patients with ulcerative colitis, adsorptive depletion of granulocytes and monocytes impacts mucosal level of neutrophils and clinically is most effective in steroid naïve patients. Dig Liver Dis. 2008;40:731–6.

    Article  CAS  PubMed  Google Scholar 

  107. Yokoyama Y, Kawai M, Fukunaga K, et al. Looking for predictive factors of clinical response to adsorptive granulocyte and monocyte apheresis in patients with ulcerative colitis: markers of response to GMA. BMC Gastroenterol. 2013;13:27.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Yokoyama Y, Watanabe K, Ito H, et al. Factors associated with treatment outcome and long-term prognosis of patients with ulcerative colitis undergoing selective depletion of myeloid lineage leukocytes: a prospective multicenter study. Cytotherapy. 2015;17:680–8.

    Article  PubMed  Google Scholar 

  109. Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER. The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009;330:864–75.

    Article  CAS  PubMed  Google Scholar 

  110. Sacco R, Tanaka T, Yamamoto T, Bresci G, Saniabadi AR. Adacolumn leucocytapheresis for ulcerative colitis: clinical and endoscopic features of responders and unresponders. Expert Rev Gastroenterol Hepatol. 2014;27:1–7.

    Google Scholar 

  111. Yamamoto T, Umegae S, Matsumoto K. Long-term clinical impact of early introduction of granulocyte and monocyte adsorptive apheresis in new onset, moderately active, extensive ulcerative colitis. J Crohns Colitis. 2012;6:750–5.

    Article  PubMed  Google Scholar 

  112. Evans RC, Clarke L, Heath P, Stephens S, Morris AI, Rhodes JM. Treatment of ulcerative colitis with an engineered human anti-TNF-alpha antibody CDP571. Aliment Pharmacol Ther. 1997;11:1031–5.

    Article  CAS  PubMed  Google Scholar 

  113. Kruis W, Nguyen GP, Morgenstern J. Granulocyte/monocyte adsorptive apheresis in moderate to severe ulcerative colitis—effective or not? Digestion. 2015;92:39–44.

    Article  CAS  PubMed  Google Scholar 

  114. Takahashi H, Sugawara K, Sugimura M, Iwabuchi M, Mano Y, Ukai K, et al. Flare up of ulcerative colitis during pregnancy treated by adsorptive granulocyte and monocyte apheresis: therapeutic outcomes in three pregnant patients. Arch Gynecol Obstet. 2013;288:341–7.

    Article  CAS  PubMed  Google Scholar 

  115. Danese S, Panés J. Development of drugs to target interactions between leukocytes and endothelial cells and treatment algorithms for inflammatory bowel diseases. Gastroenterology. 2014;147(5):981–9.

    Article  CAS  PubMed  Google Scholar 

  116. Bamias G, Clark DJ, Rivera-Nieves J. Leukocyte traffic blockade as a therapeutic strategy in inflammatory bowel disease. Curr Drug Targets. 2013;14:1490–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Löwenberg M, D'Haens G. Next-generation therapeutics for IBD. Curr Gastroenterol. 2015;17:444.

    Google Scholar 

  118. Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, et al. Oral fingolimod FTY720 for relapsing multiple sclerosis. N Engl J Med. 2006;14(355):1124–40.

    Article  Google Scholar 

  119. Cohen JA, Khatri B, Barkhof F, Comi G, Hartung HP, Montalban X, et al. Long-term up to 4.5 years; treatment with fingolimod in multiple sclerosis: results from the extension of the randomized TRANSFORMS study. J Neurol Neurosurg Psychiatry. 2015 June 25. pii: jnnp-2015-310597.

    Google Scholar 

  120. Daniel C, Sartory N, Zahn N, Geisslinger G, Radeke HH, Stein JM. FTY720 ameliorates Th1-mediated colitis in mice by directly affecting the functional activity of CD4 + CD25+ regulatory T cells. J Immunol. 2007;178:2458–68.

    Article  CAS  PubMed  Google Scholar 

  121. D’Ovidio V, Meo D, Gozer M, Bazuro ME, Vernia P. Ulcerative colitis and granulocyte-monocyte-apheresis: safety and efficacy of maintenance therapy during pregnancy. J Clin Apher. 2015;30(1):55–7.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan

    Takanori Kanai M.D.

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  1. Takanori Kanai M.D.
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Correspondence to Takanori Kanai M.D. .

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  1. Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Charité Medical School—Humboldt-University of Berlin, Berlin, Germany

    Daniel C. Baumgart

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Kanai, T. (2017). Leukocytapheresis Therapy of Inflammatory Bowel Disease. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Cham. https://doi.org/10.1007/978-3-319-33703-6_49

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  • DOI: https://doi.org/10.1007/978-3-319-33703-6_49

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