Clinical and immunological effects of adsorptive myeloid lineage leukocyte apheresis in patients with immune disorders

Abstract

Adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn is an extracorporeal treatment, which uses cellulose acetate (CA) beads as adsorptive leukocytapheresis carriers designed to remove elevated and potentially activated myeloid lineage leukocytes. Reports on the clinical efficacy of GMA in patients with skin lesions have appeared in the published work. Dermatological diseases, which are known to respond to GMA, include pyoderma gangrenosum, skin lesions of Behçet's disease, rheumatoid arthritis, pustular psoriasis, psoriatic arthritis, adult-onset Still's disease, Sweet's syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus rashes. In association with clinical studies, efforts to understand the mechanisms of GMA have made significant progress. GMA selectively depletes elevated myeloid lineage leukocytes through binding between blood immunoglobulin G or complement iC3b, which form on the surface of CA beads and the Fcγ receptors or complement receptors expressed on the myeloid lineage cells. However, GMA has immunomodulatory effects including down-modulation of inflammatory cytokine profile, changes in leukocyte surface receptors and induction of regulatory T cells. These actions render GMA a unique non-pharmacological treatment option for patients with chronic dermatoid conditions, which are difficult to treat with pharmacological preparations.

Observation of Granulocyte Adsorption in Adacolumn Cellulose Acetate Beads after Granulocytapheresis

“…We later observed that after forming the projections, the granulocytes appeared to adhere to or become incorporated into the clay‐like layer, so it appears that the granulocytes become stuck in the clay‐like layer. From our surface and cross‐sectional observations of the bead surface layer, we could not verify the assumption that spherical granulocytes were adsorbed by the surface layer through an immunological mechanism ). We could confirm, however, that granulocytes attached to the surface layer lying above the clay‐like adsorption layer, and that those granulocytes appeared to become deformed and get trapped in the clay‐like layer.…”

Observation of Granulocyte Adsorption in Adacolumn Cellulose Acetate Beads after Granulocytapheresis

“…We later observed that after forming the projections, the granulocytes appeared to adhere to or become incorporated into the clay‐like layer, so it appears that the granulocytes become stuck in the clay‐like layer. From our surface and cross‐sectional observations of the bead surface layer, we could not verify the assumption that spherical granulocytes were adsorbed by the surface layer through an immunological mechanism ). We could confirm, however, that granulocytes attached to the surface layer lying above the clay‐like adsorption layer, and that those granulocytes appeared to become deformed and get trapped in the clay‐like layer.…”

Evaluation of Neutrophil Activity Before and After Granulocyte and Monocyte Adsorptive Apheresis in Patients With Pustular Psoriasis

“…The mechanisms underlying GMA have been investigated extensively. GMA not only removes activated neutrophils and monocytes but also induces functional changes to leukocytes that pass through the column, resulting in the inhibition of neutrophil activity [18].…”

Efficacy and Safety of Upadacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction for Intractable Ulcerative Colitis

“…Next, GMA with Adacolumn ® (JIMRO, Takasaki, Japan) offers an efficacious and safe therapeutic option for patients with immune-mediated diseases such as mild-to-moderate UC and pyoderma gangrenosum that prove refractory to pharmacotherapy [29,30]. The column in GMA selectively traps activated granulocytes by binding Mac-1 expressed on the granulocytes to iC3b on beads [31]. In addition, immunoglobulin G on cellulose acetate beads mediates adsorption through Fcγ receptors on myeloid-lineage cells.…”

Observation of Granulocyte Adsorption in Adacolumn Cellulose Acetate Beads after Granulocytapheresis

“…We later observed that after forming the projections, the granulocytes appeared to adhere to or become incorporated into the clay‐like layer, so it appears that the granulocytes become stuck in the clay‐like layer. From our surface and cross‐sectional observations of the bead surface layer, we could not verify the assumption that spherical granulocytes were adsorbed by the surface layer through an immunological mechanism ). We could confirm, however, that granulocytes attached to the surface layer lying above the clay‐like adsorption layer, and that those granulocytes appeared to become deformed and get trapped in the clay‐like layer.…”

Evaluation of Neutrophil Activity Before and After Granulocyte and Monocyte Adsorptive Apheresis in Patients With Pustular Psoriasis

“…The mechanisms underlying GMA have been investigated extensively. GMA not only removes activated neutrophils and monocytes but also induces functional changes to leukocytes that pass through the column, resulting in the inhibition of neutrophil activity [18].…”

Efficacy and Safety of Upadacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction for Intractable Ulcerative Colitis

“…Next, GMA with Adacolumn ® (JIMRO, Takasaki, Japan) offers an efficacious and safe therapeutic option for patients with immune-mediated diseases such as mild-to-moderate UC and pyoderma gangrenosum that prove refractory to pharmacotherapy [29,30]. The column in GMA selectively traps activated granulocytes by binding Mac-1 expressed on the granulocytes to iC3b on beads [31]. In addition, immunoglobulin G on cellulose acetate beads mediates adsorption through Fcγ receptors on myeloid-lineage cells.…”

Observation of Granulocyte Adsorption in Adacolumn Cellulose Acetate Beads after Granulocytapheresis

“…We later observed that after forming the projections, the granulocytes appeared to adhere to or become incorporated into the clay‐like layer, so it appears that the granulocytes become stuck in the clay‐like layer. From our surface and cross‐sectional observations of the bead surface layer, we could not verify the assumption that spherical granulocytes were adsorbed by the surface layer through an immunological mechanism ). We could confirm, however, that granulocytes attached to the surface layer lying above the clay‐like adsorption layer, and that those granulocytes appeared to become deformed and get trapped in the clay‐like layer.…”

Evaluation of Neutrophil Activity Before and After Granulocyte and Monocyte Adsorptive Apheresis in Patients With Pustular Psoriasis

“…The mechanisms underlying GMA have been investigated extensively. GMA not only removes activated neutrophils and monocytes but also induces functional changes to leukocytes that pass through the column, resulting in the inhibition of neutrophil activity [18].…”

Efficacy and Safety of Upadacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction for Intractable Ulcerative Colitis

“…Next, GMA with Adacolumn ® (JIMRO, Takasaki, Japan) offers an efficacious and safe therapeutic option for patients with immune-mediated diseases such as mild-to-moderate UC and pyoderma gangrenosum that prove refractory to pharmacotherapy [29,30]. The column in GMA selectively traps activated granulocytes by binding Mac-1 expressed on the granulocytes to iC3b on beads [31]. In addition, immunoglobulin G on cellulose acetate beads mediates adsorption through Fcγ receptors on myeloid-lineage cells.…”