High Production of IL-18 by Dendritic Cells Induced by Sera from Patients with Primary Antibody Deficiency

Predominantly antibody deficiencies are a category of primary immunodeficiency diseases, which consist of several rare disorders such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA). We evaluated the effects of CVID and XLA patients’ sera as a source of microenviromental factors on maturation and function of monocyte-derived DCs. Blood was collected from 10 CVID and 5 XLA patients before immunoglobulin replacement therapy and also from 8 healthy volunteers in order to obtain necessary sera for this study. Monocyte derived DCs were generated from blood cells obtained from healthy volunteers in the presence of GM-CSF, IL-4 and 10% serum concentrations from cases and controls. Immature DCs were incubated with monocyte conditioned medium (MCM) and TNF-α in order to generate mature DCs. Interleukin 18 (IL-18) production by CD40L-activated mature DCs was measured after 24 hours of culture in vitro. IL-18 production by DCs generated in the presence of CVID and XLA patients’ sera were 6.75±2.59 and 7.08±1.75 ng/ml, respectively, which were significantly higher than normal serum conditioned DCs (3.55±0.68) ng/ml. These results suggest that the sera of patients with predominantly antibody deficiencies may contain soluble factor(s) that can induce a significant increase in IL-18 production by DCs.