Granulocyte and monocyte adsorption apheresis is effective for refractory netrophilic disorders and induces myeloid-derived suppressor cells

Takuro Kanekura, Masanao Sakanoue, Yuko Higashi
Department of Dermatology, Kagoshima University, Kagoshima, Japan

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.