Treatment of pustular psoriasis with granulocyte and monocyte adsorption apheresis
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Keywords:
Monocyte
Generalized pustular psoriasis
Plateletpheresis
Blood product
Blood component
Leukapheresis
Blood collection
Transfusion medicine
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Generalized pustular psoriasis
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Abstract: We have studied the effects of granulocyte apheresis in 18 patients with ulcerative colitis and 6 with Crohn's disease who had failed to respond to conventional therapy. Patients were treated with weekly apheresis using a granulocyte removal column (GI, Otsuka Pharmaceutical Co., Ltd., London, U.K.). We found a mean reduction in circulating granulocytes of 1.29 × 10 9 cells/L with no significant alterations in red blood cell monocyte, total lymphocyte, absolute T‐helper, or T‐cytotoxic lymphocyte counts. There were no significant changes in complement levels or immunoglobulin subclasses. There was a signifycant increase in granulocyte adhesion and a reduction in L‐selectin expression. The removal of granulocytes is unlikely to explain the effect of granulocytapheresis. The markedly increased expression of α m integrin/Mac‐1 and low L‐selectin expression alter the capability of granulocytes to migrate to sites of inflammation and may be responsible for the improvement observed in patients treated with granulocyte apheresis.
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Leukapheresis
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Generalized pustular psoriasis
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Abstract: To elucidate the molecular mechanisms involved in the therapeutic effects of granulocyte/monocyte adsorption apheresis, changes were investigated in the cytokine responses of peripheral blood mononuclear cells (PBMC) before and after granulocyte/monocyte adsorptive apheresis in ulcerative colitis (UC) patients. Four patients with active UC were enrolled. All patients responded to granulocyte/monocyte adsorptive apheresis. A total of 20 sessions of four patients were analyzed. Peripheral blood mononuclear cells were isolated from peripheral venous blood within 5 min before and after each session of granulocyte/monocyte adsorptive apheresis. The cells were stimulated with interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α for 24 h, and the secreted IL‐8 and IL‐6 levels were determined by enzyme‐linked immunosorbent assay (ELISA). IL‐1β‐induced IL‐8 and IL‐6 secretion was significantly decreased after granulocyte/monocyte adsorptive apheresis. TNF‐α‐induced IL‐8 secretion was also significantly decreased after apheresis, but there was no significant difference in TNF‐α‐induced IL‐6 secretion ( P = 0.052). In conclusion, granulocyte/monocyte adsorptive apheresis down‐regulates the IL‐1β‐ and TNF‐α‐induced inflammatory responses in PBMC. The induction of hyporesponsiveness to pro‐inflammatory cytokines may be an important factor mediating the clinical effects of granulocyte/macrophage adsorptive apheresis in UC patients.
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Neutrophilic dermatoses are a group of skin disorders characterized by intense epidermal and/or dermal inflammatory infiltrates composed of neutrophils with no evidence of infection [1]. They are often associated with ulcerative colitis and Crohn's disease [2, 3].Granulocyte and monocyte adsorptive apheresis (GMA) is an extracorporeal circulation therapy that effectively removes activated granulocytes and monocytes from peripheral blood to correct imbalances in immunological regulatory mechanisms. [...]
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Granulocyte and monocyte adsorption apheresis (GMA) is an extracorporeal apheresis unit designed to remove pathogenic myeloid lineage cells.GMA involves a column containing cellulose acetate (CA) beads that serve as adsorptive leukocyte apheresis carriers.Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population comprised of cells at several stages of myeloid lineage differentiation, that differentiate into macrophages, neutrophils, and dendritic cells.MDSCs play an important role in the regulation of the immune response and have immunosuppressive and anti-inflammatory properties.We previously demonstrated that CA beads activate complement component (iC3b).Recently, iC3b was shown to induce differentiation of myeloid cells to MDSCs.Based on these facts, we hypothesized that GMA induces MDSC differentiation.The purpose of this study was to investigate the clinical effectiveness of GMA for neutrophilic skin diseases and related arthropathy including pustular psoriasis and psoriatic arthritis and whether GMA induces MDSC.For the assessment of clinical effectiveness, 68 patients with skin lesions and 41 with arthropathy were enrolled.Skin and joint lesions were assessed by overall lesional assessment (OLA) and visual analog scale (VAS), respectively.The incidence of MDSCs was analyzed by FACS in 8 patients and the effect of GMA on MDSC induction was examined using an in vitro mini-column system that mimics GMA.GMA was effective in 57 of 68 patients (83.8%) with skin lesions and 36 of 41 (87.8%) with arthropathy.The incidence of MDSCs in the patients was significantly increased by GMA.In the in vitro mini-column system, MDSCs were induced in the blood of 5 healthy volunteers and the induction was inhibited by inactivation of iC3b.In conclusion, GMA is effective for neutrophilic disorders and the effect might be attributed, at least in part, to the induction of MDSCs via iC3b activation by the CA beads in the GMA column.± ± 8 4 7 7 ± 4 1 1 1 6 7 9 1 ± 2 1 4 6 ± ± 6 0 3 2 ± 4 0 5 5 ± 2 0 2 8 ± ± 2 .6 7 ± 5 .0 9 0 .7 0 ± μ μ
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Myeloid-derived Suppressor Cell
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