Yuji Naito ¹, Tomohisa Takagi, Toshikazu Yoshikawa

J Gastroenterol  2007 Oct;42(10):787-98. doi: 10.1007/s00535-007-2096-y. Epub 2007 Oct 15.

Neutrophil accumulation within epithelial crypts and in the intestinal mucosa directly correlates with clinical disease activity and epithelial injury in inflammatory bowel disease (IBD). Current advances have defined the mechanisms by which neutrophils are activated or migrate across endothelial and mucosal epithelial cells. A better understanding of this process will likely provide new insights into novel treatment strategies for IBD. Especially, activated neutrophils produce reactive oxygen and nitrogen species and myeloperoxidase within intestinal mucosa, which induce oxidative stress. Posttranslational modification of proteins generated by these reactive species serves as a “molecular fingerprint” of protein modification by lipid peroxidation-, nitric oxide-, and myeloperoxidase-derived oxidants. Measurement of these modified proteins may serve both as a quantitative index of oxidative stress and an important new biological marker of clinical relevance to IBD. We have succeeded in the clinical development of a novel granulocyte adsorptive apheresis therapy for IBD. In this review, we discuss current advances in defining the role of neutrophil-dependent oxidative stress in IBD.

https://pubmed.ncbi.nlm.nih.gov/17940831/

Midori Hasegawa ¹, Chikako Nishii, Nao Kabutan, Masao Kato, Atsushi Ohashi, Shigeru Nakai, Kazutaka Murakami, Makoto Tomita, Kunihiro Nabeshima, Yoshiyuki Hiki, Hisaji Oshima, Satoshi Sugiyama, Ther Apher Dial. 2007 Oct;11(5):337-40.

From these results, the inhibition of TNF action and removal of degranulated granulocytes appear to be related to the mechanism whereby cytapheresis can exert a beneficial and therapeutic function in the treatment of MPO-ANCA-associated vasculitis.

https://pubmed.ncbi.nlm.nih.gov/17845393/

J. Muñoz, M. Clavo, O. Garcia, D. Reina, A. Vidaller, R. Lafuente & L. I. Massuet

ISBT Science Series (2007) 2, 96–101

There is a strong basis to support the modulators properties of innate immunity of GCAP, although there is a lack of data that explains deeply the interactions between the mechanisms involved. GMA may represent a new therapy that offers not a single pathway effect but a global modulation of the most important pathways involved in innate immune response. Future investigations should elucidate the intimate mechanism of action.

https://www.researchgate.net/publication/239319651_Adsorptive_monocyte_and_granulocyte_apheresis_in_the_chronic_inflammatory_illness_ulcerous_colitis_Crohn’s_disease_rheumatoid_arthritis_and_Behcet_syndrome

Midori Hasegawa ¹, Atsushi Ohashi, Nao Kabutan, Saori Hiramatsu, Masao Kato, Kazutaka Murakami, Makoto Tomita, Kunihiro Nabeshima, Yoshiyuki Hiki, Satoshi Sugiyama, Ther Apher Dial. 2006 Oct;10(5):412-8.

 From these results, cytapheresis can be considered a safe and effective treatment for MPO-ANCA-associated vasculitis. As for the mechanism of its action, soluble tumor necrosis factor receptor 1 (sTNFR), sTNFR2 and interleukin 1 receptor antagonist were elevated soon after cytapheresis and those levels 2 h after the cytapheresis procedure were higher than before the procedure in some cases. These elevations might be related to the efficacy of cytapheresis.

https://pubmed.ncbi.nlm.nih.gov/17096695/

Shoichi Nishise ¹, Yuji Takeda, Hiroaki Takeda, Katsuyoshi Ishihama, Tadahisa Fukui, Sumio Kawata, Dig Dis Sci. 2006 May;51(5):934-41.

These results suggested that bound complement fragment (e.g., C3b) on CA beads plays a central role in granulocyte adsorption to CA beads and that C3a and C5a augment the release of anti-inflammatory substances. We therefore conclude that complement activation is involved in these biological responses of leukocyte apheresis

https://pubmed.ncbi.nlm.nih.gov/16642423/

Takuro Kanekura ¹, Katsuya Hiraishi, Koichi Kawahara, Ikuro Maruyama, Tamotsu Kanzaki

Ther Apher Dial 2006 Jun;10(3):247-56. doi: 10.1111/j.1744-9987.2006.00369.x.

In the present study, we have shown that granulocyte and monocyte adsorption apheresis (GCAP), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is useful for skin diseases attributable to activated granulocytes and psoriatic arthritis (PsA). We assessed the clinical effectiveness of GCAP and investigated the mechanisms underlying the adsorption of pathogenic granulocytes. The effect of GCAP was assessed in 14 patients with neutrophilic dermatoses and 16 with PsA. The mechanisms by which the instrument adsorbs activated granulocytes were investigated using an in vitro mini-column system that mimics the GCAP. Skin lesions and arthropathy improved in 22 of 29 patients (75.9%) and 14 of 18 (77.8%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, increased compared with normal subjects, was reduced by GCAP. In the mini-column system, CA beads adsorbed 50% neutrophils; and adsorption was inhibited significantly by treating plasma with EDTA and blood cells with antihuman CD11b monoclonal antibody. GCAP was useful for treating neutrophilic dermatoses and PsA. GCAP adsorbs Mac-1-expressing neutrophils to the CA beads by the binding of complement component (iC3b) on CA beads and CD11b expressed on activated neutrophils.

https://pubmed.ncbi.nlm.nih.gov/16817789/

Mitsuhiko Moriyama ¹, Miki Kaneko, Hiroshi Matsumura, Akiko Fukushima, Hiroshi Aoki, Naohide Tanaka, Kazumichi Kuroda, Kazufumi Shimizu, Katsuya Hiraishi, Yasuyuki Arakawa, Intervirology. 2005;48(2-3):84-8.

Our in vitro study confirmed that G-1 beads adsorbed HCV; therefore, apheresis using a column filled with G-1 beads may reduce the HCV RNA load in the blood of patients with chronic hepatitis C.

https://pubmed.ncbi.nlm.nih.gov/15812179/

Wolfgang Ramlow ¹, Jorg Emmrich, Peter Ahrenholz, Gisela Sparmann, Nobuhito Kashiwagi, Marita Franz, Takashi Yokoyama, Toshikazu Yoshikawa, J Clin Apher. 2005 Jul;20(2):72-80.

Adacolumn is a medical device for adsorptive cytapheresis. It has been developed for selective adsorption of granulocytes and monocytes from peripheral blood of patients with immune disorders, such as autoimmune diseases and chronic inflammatory diseases. A double blind sham-controlled crossover study design was used in order to evaluate in vivo biological responses of leukocytes as well as biocompatibility during and after Adacolumn cytapheresis in healthy volunteers.

https://pubmed.ncbi.nlm.nih.gov/15892085/

Abbi R. Saniabadi, Hiroyuki Hanai, Yasuo Suzuki, Toshihide Ohmori, Koji Sawada, Naoki Yoshimura, Yasushi Saito, Yuji Takeda, Kazuo Umemura, Kazunao Kondo, Yasuhiko Ikeda, Ken Fukunaga, Mitsuyoshi Nakashima, Alberto Beretta, Ingvar Bjarnason, Robert Lofberg, https://doi.org/10.1002/jca.20046

In conclusion, selective depletion of myeloid cells appears to induce anti-inflammatory effects and represents a non-pharmacological treatment for patients with active IBD. The treatment has a clear drug-sparing role. Changes in blood levels of inflammatory and anti-inflammatory factors are thought to contribute to the efficacy of this procedure.

https://onlinelibrary.wiley.com/doi/abs/10.1002/jca.20046

Y Takeda ¹, K Hiraishi, H Takeda, N Shiobara, H Shibusawa, A R Saniabadi, M Adachi, S Kawata, Inflamm Res. 2003 Jun;52(7):287-90.

These results indicate that CA beads selectively induce IL-1ra release from leucocytes which should contribute to the anti-inflammatory effect of granulocyte and monocyte adsorptive apheresis with CA beads as apheresis carriers.

https://pubmed.ncbi.nlm.nih.gov/12861393/