Natural Killer Cell Frequency and Serum Cytokine Levels in Monoclonal Gammopathies: Correlation of Bone Marrow Granular Lymphocytes to Prognosis

Abstract

The percent of granular lymphocytes of total bone marrow lymphocytes was 12.5% in controls, 15% in myeloma and 27% in monoclonal gammopathy of undetermined significance (MGUS). A good correlation was found between the percent of granular lymphocytes in the bone marrow lymphocytes at diagnosis (Y) and the years of survival (X) from the diagnosis of either the IgG- or IgA-type myeloma. The linear regression equation calculated for the IgG-type myeloma was Y = 1.6X + 7.42, and for the IgA-type myeloma Y = 4.25X + 4.75. For the purpose of analyzing in detail the granular lymphocyte behavior, two-color analyses of peripheral blood mononuclear cells and the serum levels of cytokines were performed. The absolute number of CD3+ cells, CD4+CD45RA+ cells and CD4+CD29+ cells was lower in the multiple myeloma (MM) cases than that of MGUS or controls (p < 0.01). The CD57+CD16+ natural killer (NK) cells were lower in MM cases than in MGUS cases. The serum levels of IL-1, which may activate NK cells, were higher in the MGUS cases than in either myeloma cases or controls (p < 0.01). The IL-10 levels, which may inhibit the proliferation of NK cells, were higher in the myeloma cases than in the MGUS cases (p < 0.05). Detailed understanding of the cytokine network of myeloma patients and their NK cell frequency may be important for the investigation of M proteinemias and for the future strategic planning of biological modulation therapies of myeloma patients.