R Sanmartí ¹, S Marsal, J Valverde, E Casado, R Lafuente, N Kashiwagi, J-R Rodriguez-Cros, A Erra, D Reina, J Gratacós Rheumatology (Oxford) 2005 Sep;44(9):1140-4. doi: 10.1093/rheumatology/keh701. Epub 2005 May 31.

Objective: To assess the efficacy and safety of adsorptive granulocyte and monocyte apheresis (GCAP) in patients with refractory rheumatoid arthritis (RA). Methods: Patients with active and refractory RA were treated with weekly GCAP sessions using a column filled with acetate beads (Adacolumn) over five consecutive weeks. Clinical assessments and response to therapy were analysed at weeks 5, 7, 12 and 20 in an open multicentre trial. The primary outcome measure of clinical response was 20% improvement in the American College of Rheumatology criteria (ACR20) at week 20. EULAR (European League Against Rheumatism) response criteria, based on the disease activity score for 28 joints (DAS28) and disability using the Health Assessment Questionnaire (HAQ), were also assessed. Results: Of 27 patients, 81.5% were women with mean disease duration of 14.4 yr. The mean number of previous disease-modifying antirheumatic drugs (DMARDs) was 3.7, and 48.1% of patients had previously failed on biologicals. On an intention-to-treat basis, 40.7% of patients achieved an ACR20 and 44.4% a therapeutic EULAR response at week 20. These percentages were 50 and 54.5% in 22 patients who completed the trial. In the 10 completers who had previously failed on biologicals, an ACR response was achieved in four patients (ACR20, two; ACR50, one; ACR70, one). A significant decrease was recorded in different ACR response components, including the tender joint and swollen joint counts, pain score and patient and physician global disease assessments, as well as the DAS28 index; most of them improved after week 5. ESR and CRP, but not the HAQ score, had decreased significantly at week 20. The treatment was well tolerated and only one serious adverse event related to the study procedure was documented (sepsis due to a catheter infection). Conclusions: GCAP treatment led to significant clinical improvement in a subset of patients with RA who had failed to respond to DMARDs or biologicals. Further large, placebo-controlled studies are warranted to fully assess the therapeutic value of GCAP for refractory RA.

https://pubmed.ncbi.nlm.nih.gov/15927997/

https://academic.oup.com/rheumatology/article/44/9/1140/1784472?login=false

Ritsuko Yanaru-Fujisawa, Takayuki Matsumoto, Shotaro Nakamura, Shuji Kochi, Mitsuo Iida, Futoshi Kohda, Minako Hirahashi, Takashi Yao, Ryuichi Mibu Case Reports Inflamm Bowel Dis. 2005 Aug;11(8):780 DOI: 10.1097/01.mib.0000172558.39767.b7

https://pubmed.ncbi.nlm.nih.gov/16043996/

Shinya Mori MD,Masakazu Nagashima MD,Kazuhiro Yoshida MD,Kouji Yoshino MD,Mikako Aoki MD,Seiji Kawana MD,Ichiro Hirata BSc,Abby Saniabadi PhD, Shinichi Yoshino MD, International journal of Dermatology First published: 06 April 2004

GMA, which depletes activated neutrophils and monocytes/macrophages, appears to be effective for inflammatory skin ulcers which do not respond to conventional medications.

https://onlinelibrary.wiley.com/doi/10.1111/j.1365-4632.2004.01986.x

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/

K Yamaji ¹, H Tsuda, H Hashimoto Ther Apher  2001 Aug;5(4):287-92. doi: 10.1046/j.1526-0968.2001.00358.x.

Cytapheresis has been investigated recently for the treatment of autoimmune related diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis, and so on. A large number of physicians have indicated that patients with autoimmune diseases respond to cytapheresis treatment. The effective mechanism of cytapheresis for immune disorders is still controversial. However, the removal of the leukocyte including granulocyte, lymphocyte, and monocyte may play a crucial role in correcting imbalance of the immune system. A session of cytapheresis including leukocytapheresis (LCAP) and granulocytapheresis (GCAP) may not create a sufficient amount of cell removal for the human body. However, the cell removal can be a trigger of the immunomodulation as the treatment for immune disorder. Furthermore, not only cell removal but also reaction by blood contacting with medical device materials may play a role as an immunomodulation for immune disorders. This review introduces current cytapheresis technologies and attempts to elucidate the effective mechanism of cytapheresis for immune disorders, focused on LCAP and/or GCAP for RA or IBD.

https://pubmed.ncbi.nlm.nih.gov/11724514/

N Kashiwagi ¹, I Hirata, R Kasukawa

Ther Apher. 1998 May;2(2):134-41. doi: 10.1111/j.1744-9987.1998.tb00091.x.

Rheumatoid arthritis (RA) is an inflammatory condition, the etiology of which is not well understood. Recent reports indicate a major role of granulocytes in the pathogenesis of RA; arthritic joints are infiltrated with phagocytic leukocytes, granulocytes, and monocytes/macrophages, and it is believed that these cells, by releasing degradative proteinases, cytokines, and reactive oxygen species, contribute to joint destruction. Hence, the apheresis of granulocytes and monocytes may benefit patients with RA. Granulocyte and monocyte apheresis was carried out in 143 patients with RA using an apheresis column (G-1) packed with 220 g cellulose acetate beads, which selectively adsorb granulocytes and monocytes. Patients received 1 or 2 apheresis sessions, each of 1 h duration per week over a 4 week period at a flow rate of 30 ml/min. Apheresis significantly reduced swollen and tender joint counts and the duration of morning stiffness, and it increased grip strength, together with suppression of tumor necrosis factor-alpha and interleukin-1beta production by peripheral blood monocytes. It is concluded that this alternative treatment induces a kind of immunomodulation.

https://pubmed.ncbi.nlm.nih.gov/10225715/

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

N Kashiwagi ¹, I Hirata, R Kasukawa

Ther Apher. 1998 May;2(2):134-41. doi: 10.1111/j.1744-9987.1998.tb00091.x.

Rheumatoid arthritis (RA) is an inflammatory condition, the etiology of which is not well understood. Recent reports indicate a major role of granulocytes in the pathogenesis of RA; arthritic joints are infiltrated with phagocytic leukocytes, granulocytes, and monocytes/macrophages, and it is believed that these cells, by releasing degradative proteinases, cytokines, and reactive oxygen species, contribute to joint destruction. Hence, the apheresis of granulocytes and monocytes may benefit patients with RA. Granulocyte and monocyte apheresis was carried out in 143 patients with RA using an apheresis column (G-1) packed with 220 g cellulose acetate beads, which selectively adsorb granulocytes and monocytes. Patients received 1 or 2 apheresis sessions, each of 1 h duration per week over a 4 week period at a flow rate of 30 ml/min. Apheresis significantly reduced swollen and tender joint counts and the duration of morning stiffness, and it increased grip strength, together with suppression of tumor necrosis factor-alpha and interleukin-1beta production by peripheral blood monocytes. It is concluded that this alternative treatment induces a kind of immunomodulation.

https://pubmed.ncbi.nlm.nih.gov/10225715/

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1744-9987.1998.tb00091.x?sid=nlm%3Apubmed