Tsukasa Nakamura ¹, Yasuhiko Kawagoe, Takaharu Matsuda, Akiko Ueda, Yoshihiko Ueda, Yutaka Takahashi, Araki Tanaka, Hikaru Koide Blood Purif  2004;22(6):499-504. doi: 10.1159/000081896. 

Background/aim: Increases in microalbuminuria and endothelin (ET-1) are involved in the development of ulcerative colitis (UC) and in its progress. Because granulocyte and monocyte adsorption apheresis has proven to be useful in the treatment of UC, we examined whether urinary albumin excretion and plasma ET-1 concentrations are altered and whether granulocyte and monocyte adsorption apheresis affects the concentrations of these two factors in patients with active UC. Methods: Twenty patients with active UC and 20 age-matched healthy volunteers (our hospital staffs) were included in this study. UC patients were randomly divided into two treatment groups: a granulocyte and monocyte adsorption treatment group (n = 10) and a conventional treatment group (n = 10). The urine albumin/creatinine ratio, plasma ET-1 concentration and tumor necrosis factor (TNF)-alpha were determined before and after treatment and compared between 2 treatment groups. The 10 adsorption treatment patients underwent 5 consecutive weekly apheresis sessions, each of 60 min duration at a flow rate of 30 ml/min. Results: The urine albumin/creatinine ratio in UC patients (6.4 +/- 2.2 mg/mmol) were higher than that in healthy subjects (1.0 +/- 0.7 mg/mmol, p < 0.01). In addition, the plasma ET-1 level in UC patients (3.5 +/-1.5 pg/ml) was higher than that in healthy subjects (0.8 +/- 0.4 pg/ml, p < 0.01). Plasma TNF-alpha was detected in UC patients (18.8 +/- 8.4 pg/ml), but not in healthy subjects. The urine albumin/creatinine ratio was highly correlated with the plasma ET-1 level (r = 0.62; p < 0.01) and plasma TNF-a level (r = 0.66, p < 0.01). Granulocyte and monocyte adsorption apheresis reduced the urine albumin/ creatinine ratio from 6.6 +/- 2.4 to 1.8 +/- 0.6 mg/mmol (p < 0.01), reduced the plasma ET-1 level from 3.7 +/- 1.6 to 1.4 +/- 0.6 pg/ml (p < 0.05) and reduced the plasma TNF-alpha from 19.2 +/- 8.6 to 3.8 +/- 1.2 pg/ml (p < 0.01). Conventional treatment did not affect these factors. Conclusion: Our data suggest that increases in the urine albumin/creatinine ratio, ET-1 and TNF-alpha play an important role in active UC and that granulocyte and monocyte adsorption apheresis is effective in ameliorating such increases.

https://pubmed.ncbi.nlm.nih.gov/15528877/

https://www.karger.com/Article/Abstract/81896

Yukihiko Kawasaki ¹, Junzo Suzuki, Shigeo Suzuki, Hitoshi Suzuki

J Pediatr Gastroenterol Nutr. 2004 Oct;39(4):422-5. doi: 10.1097/00005176-200410000-00021.

Generally, UC is associated with intervals of acute exacerbation and the administration of corticosteroids is effective in bringing about a clinical remission (¹). Corticosteroids are not always effective even in doses over 1 mg/kg/day. In addition, the long-term use of corticosteroids often causes serious side effects such as growth retardation, glaucoma, hormonal disturbance, peptic ulcer, liver dysfunction and psychologic problems. Alternative treatment for active UC may be necessary to avoid the clinical problems associated with corticosteroid therapy. In recent years, leukocytapheresis (LCAP) and granulocytapheresis (GCAP) using a leukocyte removal filter has been found effective in some cases of adults with inflammatory bowel disease (^2,3). However, there have been few reports concerning the efficacy of LCAP and GCAP for UC in childhood (⁴).We report two children with severe steroid-dependent UC in whom LCAP with leukocyte removal filter was used in treatment. LCAP therapy was safe and effective in two children with refractory UC and allowed discontinuation of corticosteroid therapy with an improvement in quality of life. Prospective studies of this therapy will be needed to clarify the role of LCAP in treatment of childhood UC.

https://pubmed.ncbi.nlm.nih.gov/15448435/

https://journals.lww.com/jpgn/Fulltext/2004/10000/Leukocytapheresis_with_Leukocyte_Removal_Filter.21.aspx

Purushothaman Premchand ¹, Ken Takeuchi, Ingvar Bjarnason Eur J Gastroenterol Hepatol 2004 Sep;16(9):943-5. doi: 10.1097/00042737-200409000-00023.

Refractory ulcerative colitis that fails conventional intense medical treatment often leads to colectomy. Although ciclosporin and infliximab may avert colectomy in certain cases, these treatments come with substantial toxicity and may only act as a bridge to avert emergency surgery. Granulocyte monocyte/macrophage adsorption apheresis is a new treatment and has shown efficacy for refractory colitis in up to 80% of cases in a Japanese study and is apparently only associated with negligible side effects. We report a case of severe refractory proctitis destined for colectomy effectively treated with granulocyte monocyte/macrophage adsorption apheresis. After two of five sessions the patient achieved full clinical remission, which has been sustained with the addition of azathioprine for more than 1 year.

https://pubmed.ncbi.nlm.nih.gov/15316424/

Takuro Kanekura ¹, Akira Gushi, Masahiro Iwata, Seita Fukumaru, Ryoko Sakamoto, Koichi Kawahara, Ikuro Maruyama, Tamotsu Kanzaki

J Am Acad Dermatol. 2004 Aug;51(2 Suppl):S83-7. doi: 10.1016/j.jaad.2003.12.023.

The painful orogenital ulcerations of Behçet’s disease are among the major symptoms of patients and are often intractable. We assessed the efficacy of granulocyte and monocyte adsorption apheresis therapy in two patients, a 21-year-old man with orogenital ulcerations and a 50-year-old woman with genital ulceration and abdominal pain. They underwent 5 and 8 granulocyte and monocyte adsorption apheresis treatments at 5-day intervals, respectively. The painful orogenital ulcerations of the man responded dramatically and the genital ulcer of the woman decreased in size and her abdominal pain was improved. Our results demonstrate that granulocyte and monocyte adsorption apheresis may be useful for treating orogenital ulcerations of Behçet’s disease.

https://pubmed.ncbi.nlm.nih.gov/15280820/

Cuenca, F & Paredes, J & Mendoza, J & Cruz, D & Herrero, A & Díaz-Rubio, M.Revista española de enfermedades digestivas : organo oficial de la Sociedad Española de Patología Digestiva .2004,96. 501-3, 504. DOI:10.4321/S1130-01082004000700007.

Objective: To describe our experience with granulocyte apheresis to induce remission in patients with active Crohn’s disease refractory to conventional treatment. We summarize the results previously obtained with this technique.

Conclusions: Granulocyte apheresis is a safe and well tolerated therapeutic modality that can be a valid therapeutic alternative in the induction of remission in inflammatory bowel disease, although controlled clinical trials must be conducted to define long-term efficacy, as well as to establish « optimal patient » selection, re-treatment interval, and number of sessions.

https://pubmed.ncbi.nlm.nih.gov/15283632/

Kazuo Kusugami ¹, Kenji Ina, Takafumi Ando, Kenji Hibi, Yuji Nishio, Hidemi Goto, J Gastroenterol. 2004 Dec;39(12):1129-37.

Patients with inflammatory bowel disease (IBD) have intestinal and extraintestinal symptoms that can greatly impair their quality of life. They must rely on multiple medications with aminosalicylates, corticosteroids, and purine analogues to control these symptoms. Although decades of clinical experience in IBD management has led to optimized approaches for achieving the induction and maintenance of remission, the disease in some patients is still refractory to conventional medical treatment, or the effectiveness of these drugs can be limited by treatment-related side effects. Significant progress in our understanding of the pathogenesis of IBD has yielded several immunomodulatory approaches with novel biological agents or apparatus, such as cyclosporine, cytoprotective agents, infliximab, and leukocytapheresis. Further immunomodulatoy therapy, aiming at the inhibition of molecular and cellular mediators, is anticipated, in parallel with the clarification of immunoinflammatory pathways in IBD. An additional goal will be to identify factors predictive of response to treatment with each novel immunomodulatory agent or apparatus. This will help provide each patient with optimized and individualized therapy, thereby increasing therapeutic efficacy and reducing possible side effects.

https://pubmed.ncbi.nlm.nih.gov/15622475/

T Kanekura ¹, K Terasaki, Y Higashi, N Yoshii, K Kawahara, I Maruyama, T Kanzaki

Clin Exp Dermatol 2004 Jul;29(4):410-2. doi: 10.1111/j.1365-2230.2004.01502.x.

Adult Still’s disease is characterized by a high spiking fever, transient skin rash, and polyarthralgia. Joint pain is one of the major complaints and is often intractable. We assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) therapy for treating arthralgia in adult Still’s disease. A 33-year-old woman with adult Still’s disease who suffered from recalcitrant arthralgia resistant to systemic corticosteroids was treated with GCAP therapy. She underwent five GCAP treatments at 5-day intervals. Her joint pain responded dramatically to the GCAP therapy, suggesting that GCAP may be useful for treating adult Still’s disease. We present a detailed description of the patient and this novel therapy.

https://pubmed.ncbi.nlm.nih.gov/15245543/

Y. Takeda, N. Shiobara, A. R. Saniabadi, M. Adachi & K. Hiraishi, Inflammation Research volume 53, pages 277–283 (2004)

Objective: Evolving evidence of anti-inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte (GM) apheresis with a column containing cellulose acetate (CA) beads as apheresis carriers. This study was undertaken to obtain insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis with CA beads. Methods: In a series of in-vitro experiments, we investigated the effects of plasma proteins and the leucocytes β2 integrin (CD18) on granulocyte adsorption to CA beads. Results: Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1 receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were released by granulocytes that adhered to CA beads. Conclusions: Plasma IgG, C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.

https://link.springer.com/article/10.1007/s00011-004-1253-5

Takeshi Kusaka ¹, Ken Fukunaga, Kunio Ohnishi, Tadashi Kosaka, Toshihiko Tomita, Yoko Yokoyama, Koji Sawada, Yoshihiro Fukuda, Hiroto Miwa, Takayuki Matsumoto J Clin Apher. 2004;19(4):168-73. doi: 10.1002/jca.20023.

Six patients with active Crohn’s disease (CD) unresponsive to conventional medications (CM) were treated with Monocyte-granulocytapheresis (M-GCAP). CD patients who scored 200-400 points in Crohn’s disease activity index (CDAI) in spite of receiving CM, including enteral nutrition, for at least 2 weeks were enrolled in our double series trial. Each series had 5 weekly M-GCAP and 2 follow-up weeks, and each M-GCAP treated 1,800 ml of patient’s peripheral blood. After the 1st series, patients who decreased more than 50 points on the CDAI were deemed responders and enrolled in the second series. Patients with a CDAI score less than 150 points were considered in remission. The patients’ quality of life was evaluated using an index (IBDQ) before and after the 1st series. The CDAI was significantly decreased comparing before and after the 1st series (258.2 +/- 36.2 vs. 166.5 +/- 16.6; P < 0.02). 50% of patients (3/6) responded to the therapy, and one case (16.7%) could be induced to remission. Significant removal was revealed only for white blood cells (25.6 +/- 16.9%; P < 0.05), especially granulocytes (29.5 +/- 22.5%; P < 0.05). A statistically significant improvement of IBDQ was revealed in the responders’ group (162.3 +/- 17.2 vs. 189.3 +/- 11.5; P < 0.03). M-GCAP could be an effective adjunctive therapy for active CD patients unresponsive to CM allowing them to maintain a high QOL. However, it might be difficult to improve patients who could not be induced to remission after the 1st series by applying another series.

https://pubmed.ncbi.nlm.nih.gov/15597346/

Yasuo Suzuki ¹, Naoki Yoshimura, Abby R Saniabadi, Yasushi Saito

Dig Dis Sci. 2004 Apr;49(4):565-71. doi: 10.1023/b:ddas.0000026299.43792.ae.

Corticosteroid therapy of ulcerative colitis (UC) is associated with frequent adverse side effects and poor quality of life. Recently, adsorptive granulocyte and monocyte/macrophage apheresis has shown efficacy in patients with severe steroid refractory UC. The objective of this study was to investigate if, instead of corticosteroids, adsorptive leukocytapheresis has efficacy as the first-line therapy for steroid-naïve patients with active UC. Twenty patients, aged 15-49 years, with a mean clinical activity index (CAI) of 8.6 were recruited. Adsorptive leukocytapheresis was done with Adacolumn, which contains cellulose acetate beads as adsorptive carriers for granulocytes and monocytes (FcgammaR and complement receptors expressing leukocytes). Each patient received 6 to 10 leukocytapheresis sessions of 60-min duration, at 2 sessions/week. Efficacy was assessed 1 week after the last session. Post treatment, the mean CAI was 3.0 (P = 0001), and 17 of 20 patients (85%) were in remission. There were significant falls in C-reactive protein (P = 0.0003), total white cell counts (P = 0.003), neutrophils (P = 0.0029), and monocytes (P = 0.0038), an increase in lymphocytes (P = 0.001), and increases in the blood levels of soluble TNF-alpha receptors I (P = 0.0007) and II (P = 0.0045) in the column outflow (blood return to the patients). Further, at 8 months, 60% of patients had maintained their remission. No severe side effects were reported. In conclusion, adsorptive leukocytapheresis should reduce corticosteroid therapy in patients with moderate UC; cases with early-stage active disease may benefit most.

https://pubmed.ncbi.nlm.nih.gov/15185858/