Serum concentrations and clinical significance of soluble CD40 ligand in patients with multiple myeloma

Abstract

Multiple myeloma (MM) is a disease of plasma cells that express the CD40 receptor. Binding of the CD40 by its natural ligand, CD40 ligand (CD40L), produces growth arrest and/or apoptosis in MM. To evaluate serum levels of soluble CD40L (sCD40L) in MM patients and to correlate them with markers of disease activity and angiogenesis, such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), interleukin-6 (IL-6), proliferation marker Ki-67 proliferation index (Ki-67 PI) and bone marrow plasma cell infiltration, fifty-eight MM patients were studied in diagnosis and 43 of them after completion of treatment. Serum levels of sCD40L, VEGF, HGF and IL-6 were measured by ELISA, whereas Ki-67 PI and bone marrow plasma cell infiltration were measured by immunohistochemistry. Pre-treatment levels of sCD40L in MM patients were higher compared to controls and to their levels after effective treatment. Treatment regimen did not affect the degree of reduction of sCD40L levels, whereas patient in partial remission had increased levels compared to those with better response. Significant differences were found among disease stages. There were also positive correlations between CD40L with HGF, VEGF, IL-6 and Ki-67 PI. Elevated serum sCD40L is found in patients with advanced MM stage and can be reduced after effective treatment. Increased levels of this mediator are correlated with angiogenic cytokines, providing evidences that CD40L/CD40 interactions play a significant role in the mechanisms of angiogenesis in MM patients.