Toshihiko Hidaka ¹, Kimihiro Suzuki, Ther Apher Dial. 2003 Apr;7(2):161-4.

Leukocytapheresis (LCAP) is an apheresis technique for depleting pathogenic leukocytes from the circulating blood to improve the condition of the patient. LCAP sensu lato has been applied for the treatment of various rheumatic diseases: other treatments include thoracic duct drainage, photopheresis, centrifugal LCAP, granulocytapheresis (GCAP) and filtration LCAP. Among these modalities, GCAP and filtration LCAP are most commonly used in Japan for two reasons; the equipment and procedure are simple and practical and adverse events are rare and minor. In this article, LCAP, in particular filtration LCAP, for the treatment of rheumatic diseases is reviewed.

https://pubmed.ncbi.nlm.nih.gov/12918938/

Nobuhito Kashiwagi ¹, Minoru Nakano, Abby R Saniabadi, Masakazu Adachi, Toshikazu Yoshikawa

Inflammation 2002 Aug;26(4):199-205. doi: 10.1023/a:1016523914161.

In active rheumatoid arthritis, large numbers of granulocytes and macrophages are found in the inflamed joints. These leucocytes can promote inflammation and tissue injury by releasing inflammatory cytokines, proteinases and oxygen derivatives. To see if granulocyte and monocyte (GM) depletion produces anti-inflammatory effect, GM adsorption apheresis was performed in rabbits with immune arthritis by using a column (Adacolumn) filled with cellulose diacetate beads (G-1 beads) as adsorptive carriers which selectively adsorb CD11b positive GMs. Injection of ovalbumin into the knee joints of ovalbumin-sensitized rabbits caused a marked increase in peripheral blood leucocytes, joint swelling, increased granulocyte adhesion to G-1 beads and elevated TNF-alpha production by peripheral blood mononuclear cells (PBMC). When rabbits received a 60 min adsorption apheresis, there was suppression of CD11b positive leucocyte infiltration into the joint and reduced joint swelling (P < 0.01) compared with controls. Additionally, there was a significant (p < 0.01) suppression of TNF-alpha production by PBMC in the post column blood. These results suggest that GM depletion may serve as a non-pharmacological strategy to modify inflammatory disorders.

https://pubmed.ncbi.nlm.nih.gov/12184634/

Nobuhito Kashiwagi ¹, Minoru Nakano, Abby R Saniabadi, Masakazu Adachi, Toshikazu Yoshikawa

Inflammation 2002 Aug;26(4):199-205. doi: 10.1023/a:1016523914161.

In active rheumatoid arthritis, large numbers of granulocytes and macrophages are found in the inflamed joints. These leucocytes can promote inflammation and tissue injury by releasing inflammatory cytokines, proteinases and oxygen derivatives. To see if granulocyte and monocyte (GM) depletion produces anti-inflammatory effect, GM adsorption apheresis was performed in rabbits with immune arthritis by using a column (Adacolumn) filled with cellulose diacetate beads (G-1 beads) as adsorptive carriers which selectively adsorb CD11b positive GMs. Injection of ovalbumin into the knee joints of ovalbumin-sensitized rabbits caused a marked increase in peripheral blood leucocytes, joint swelling, increased granulocyte adhesion to G-1 beads and elevated TNF-alpha production by peripheral blood mononuclear cells (PBMC). When rabbits received a 60 min adsorption apheresis, there was suppression of CD11b positive leucocyte infiltration into the joint and reduced joint swelling (P < 0.01) compared with controls. Additionally, there was a significant (p < 0.01) suppression of TNF-alpha production by PBMC in the post column blood. These results suggest that GM depletion may serve as a non-pharmacological strategy to modify inflammatory disorders.

https://pubmed.ncbi.nlm.nih.gov/12184634/

M Kyogoku ¹, R Kasukawa, Inflamm Res. 1998 Oct;47 Suppl 3:S166-76.

 The results were further confirmed in the adjuvant arthritic rat model. G-1 beads adsorb some amounts of platelets at the beginning and then about a quarter of circulating neutrophils, monocytes, natural killer cells, and B cells, but not T cells. Various factors released from blood cells during transit through the column must have influenced the cells including lymphocytes which passed through the column. G-column actually eliminates some parts of aggressive leukocytes, but a more interesting story is the modification of blood components, which occurred in the G-1 column, and when returned to the patients, may have ameliorated the unbalanced homeostatic network and induced acceleration of healing

https://pubmed.ncbi.nlm.nih.gov/9831320/

M Nagashima ¹, S Yoshino, H Tanaka, N Yoshida, N Kashiwagi, A R Saniabadi

Rheumatol Int. 1998;18(3):113-8. doi: 10.1007/s002960050068.

To investigate if granulocyte and monocyte apheresis mitigates the symptoms of rheumatoid arthritis (RA), and influences production of panmyelocytes (CD15+ CD16- cells) at the bone marrow level, 27 RA patients who had elevated granulocyte counts were recruited. The granulocyte and monocyte apheresis column (G-1 column) is an extracorporeal type device packed with 220 g cellulose acetate beads to which granulocytes and monocytes specifically adhere. Patients received apheresis of 1 hr duration twice per week, 8 times over a period of 4 weeks. To prepare CD15+CD16- cells, iliac bone marrow aspirate was obtained at baseline and at 2 weeks after completion of the apheresis course. Ex-vivo proliferation of bone marrow low density cells and production of IgM-RF were also investigated. Following granulocyte and monocyte apheresis, there was a suppressed tendency in the number of CD15+CD16- cells in patients with high bone marrow CD15+CD16- cell counts at baseline. Clinical assessments 2 weeks after the completion of apheresis therapy showed improvements in swollen joint count (P < 0.001), tender joint count (P < 0.001) and duration of morning stiffness (P < 0.005). The results suggest that granulocytes and monocytes/macrophages have a pathological role in RA and apheresis treatment to reduce or suppress these cells should benefit patients with RA.

https://pubmed.ncbi.nlm.nih.gov/9833252/

https://link.springer.com/article/10.1007%2Fs002960050068

Yasuo Yanagihara,Kei Yanagisawa, Hiroshi Nishikawa,Masaaki ‘lakai,and Masahisa Kyogoku, Jpn JApheresis16 (1):187-188,1997

https://dl.ndl.go.jp/view/download/digidepo_10553960_po_ART0010209866.pdf?contentNo=1&alternativeNo=

M Ohara ¹, A R Saniabadi, S Kokuma, I Hirata, M Adachi, T Agishi, R Kasukawa, Artif Organs. 1997 Sep;21(9):989-94.

The G-1 column is an extracorporeal type granulocytapheresis device packed with 220 g cellulose acetate beads to which granulocytes and monocytes specifically adhere. A total of 59 rheumatoid arthritis patients with elevated granulocyte counts from 4 hospitals in Japan received 2 apheresis sessions of 1 h duration/week for a total of 8 times over a period of 4 weeks. About 55% of the leukocytes which entered the G-1 column were adsorbed onto the beads: 95% were granulocytes, 3.5% monocytes, and 0.4% lymphocytes. Clinical and efficacy assessments showed improvements in swollen joints (p < 0.01), tender joints (p < 0.001), the active joint score (p < 0.001), duration of morning stiffness (p < 0.01), and grip strength (p < 0.001). In good responders, the improvements were observed for up to 12 weeks following the last apheresis. Exacerbation was noted in 2 patients. It is suggested that the efficacy of the G-1 column is attributable to the removal or suppression of hyperactive leukocytes and inflammatory cytokines, inducing a kind of immunomodulation.

https://pubmed.ncbi.nlm.nih.gov/9288869/

Motoki Yonekawa ^∗Akio Kawamura^∗Takashi Komai^†Tetsuzo Agishi^‡Masakazu Adachi^§ , https://doi.org/10.1016/0955-3886(96)00030-6

In cancer and rheumatoid arthritis, granulocytosis is often observed and indicates the progress of disease. We developed a granulocytapheresis system to permit granulocyte reduction. Cellulose acetate was found to be a selective and effective adsorbent. In an in vivo study using an acetate bead column, 9.2 × 10⁸ leukocytes were collected. Initially, granulocytapheresis was applied to terminal patients or those with stage IV cancer. Pain, cough and bloody sputum were reduced in spite of no decrease in the tumor size. Granulocytapheresis appears to prevent inflammatory damage in or around the tumor site. This granulocyte reduction technique was also applied to patients with rheumatoid arthritis. The Lansbury index markedly improved after treatment. As cytokines and adhesion molecules might contribute to symptoms, granulocytapheresis may be useful in improving the “Quality of Life” in these diseases.

https://www.sciencedirect.com/science/article/abs/pii/0955388696000306

J Fujimori ¹, S Yoshino, M Koiwa, H Hirai, H Shiga, N Hayama, Y Iino, Rheumatol Int. 1996;15(5):175-80.

These findings suggested that G-1 therapy was effective for RA.

https://pubmed.ncbi.nlm.nih.gov/8717100/