Decreased periferal blood dendritic cells in multiple Myeloma: The potential role of IL-6 and Beta-2-Microglobulin

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Introduction : Several studies demonstrate the presence of quantitative and functional abnormalities in the dendritic cell (DC) subsets in patients with multiple myeloma (MM). The inhibitory effect of IL-6, TGF-!, IL-10 and beta-2-microglobuline (beta-2-MG) is highly suspected. Purpose : The aim of the study was to evaluate the myeloid and plasmacytoid dendritic cells (MDC and PDC) in newly diagnosed patients with MM in correlation with various biological markers. Materials and Methods : Thirty patients with newly diagnosed MM were included in the study. All the laboratory parameters were obtained at the time of diagnosis. Three colour flow cytometry with ILT3/lin/CD11c was used for the detection of the two peripheral blood dendritic cell (PBDC) subsets. The plasma level of IL6 was detected by ELISA (Standard Curve Range: 2-200pg/ml); the beta-2-MG- by the immunoturbidimetric test. Results : The median age of patients was 61.5 years (36-89). The mean M-protein concentration was 46.5±16.2 g/l. IgG kappa was detected in 15 patients, IgG lambda-in 4, IgA kappa-in 7, IgA lambda-in 3. The mean level of beta-2-MG was 7.0±5.7mg/l (1.82-22.49 mg/l ); beta-2-MG was used to determine the stage according to the ISS. The mean level of IL6 was 27.73±21.47pg/ml (4.6-72.5 pg/ml). The percentage of MDC and PDC was significantly lower in the periferal blood of patients with MM in comparison to healthy subjects (0.08%±0.09% vs 0.21%±0.02% and 0.04%±0.03% vs 0.16%±0.01%, respectively). A statistically significant difference was found between the percentage of MDC and PDC in the different stages. There was a negative correlation between MDC and PDC and the levels of beta-2-MG (p=0.02 and p=0.02), as well as between MDC and the IL6 levels (p=0.04). No correlation was found between MDC, PDC, levels of M-protein and the type of paraprotein. Conclusion : Our results demonstrate the relationship between peripheral blood DC, IL6 and beta-2-MG and confirm the published data for the inhibitory effect of the two factors on DC differentiation and maturation in vitro. The monitoring of beta-2-MG and IL6 may have clinical implication as a predictor of the immune system status as well as for the yield of harvested DCs for vaccination.