PHAGOCYTOSIS AND EXPRESSION OF FCg-RECEPTORS AND CD180 ON MONOCYTES IN CHRONIC LYMPHOCYTIC LEUKEMIA

Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disease characterised by accumulation of monoclonal CD19+CD5+CD23+ lymphocytes in the peripheral blood and bone marrow. CLL is the most common type of the adult leukemia in the Western world. The disease is incurable, albeit there are new molecular and immunotherapy methods currently available in conjunction with chemotherapy, leading to the "precision therapy". The majority of immunotherapeutic approaches are based on the ability of therapeutic antibodies (Rituximab, Alemtuzumab) to mobilize anti-tumour potential of the Natural Killer cells and macrophages/monocytes through their Fcg-receptors (FcγR). Therefore functional status of monocytes in CLL is an important contributor to the efficacy of this treatment. In addition, CLL patients are characterized by a profound immunodeficiency, and how this affects monocytes, has not been established. Here we study ex vivo phagocytic function and the expression of Fcg receptors and CD180 toll-like receptor (TLR) by monocytes of 14 untreated and 8 treated with Cyclophosmamide, Adriamycin, Prednisolone (COP) CLL patients, and 12 age-matched control volunteers. Phagocytic function was assessed through the ability of freshly isolated monocytes to attach and to engulf intact or opsonized Staphylococcus aureus particles in vitro with or without Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) and Interferon g (IFNg). Simultaneously, immunophenotyping for FcγRI (CD64), FcγRII (CD32), FcγRIII (CD16) and CD180 has been carried out. The results were assessed by Flow Cytometry. Our results demonstrated that phagocytosis of the intact and opsonised or intact S. aureus by monocytes of CLL patients was significantly decreased in comparison with normal controls, with no recovery upon the treatment with GM-CSF and IFNg. A significant decrease in the expression of CD64 and CD180 has been detected on monocytes of CLL patients, with the drop in CD64 expression correlating with the disease progression and advanced Rai stages. In addition, the treatment with COP led to a more profound decrease in the expression of CD64. No appreciable changes were detected in the expression of CD32 and CD16 throughout the experiments. The diminished expression of CD64 and CD180 provides possible explanation for the impaired phagocytic function of monocytes in CLL, as FcγRI receptor interaction with opsonising IgG1, and CD180 with the ligands on S. aureus might affect the ability of monocytes to attach and to engulf S. aureus particles and effectively eliminate the pathogen. Our data indicates that the decreased functional status of monocytes in CLL might contribute to the diminished efficacy of therapeutic antibodies as well as to the immunodeficiency, characteristic for these patients.