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.
Brimnes M K, I M Svane, and H E Johnsen. Impaired functionality and phenotypic profile of dendritic cells from patients with multiple myeloma. Clin Exp Immunol., 2006;144(1):76-84.
Brown RD, Pope B, Murray A, Esdale W, Sze DM, Gibson J, Ho PJ, Hart D, Joshua D. Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to upregulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta1 and interleukin-10. Blood, 2001;98:2992-8.
Butch AW, Kelly KA, Munshi NC. Dendritic cells derived from multiple myeloma patients efficiently internalize different classes of myeloma protein. Exp Hematol., 2001;29(1):85-92.
Do TH, Johnsen HE, Kjaersgaard E, Taaning E, Svane IM. Impaired circulating myeloid DCs from myeloma patients. Cytotherapy, 2004;6(3):196-203.
Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J & Liu YJ. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. Journal of Experimental Medicine, 1997;185;1101-1111.
Hart DNJ. Dendritic cells: unique leukocyte populations which control the primary immune response. Blood, 1997;90:3245-3287.
Hayashi T, Hideshima T, Akiyama M, Raje N, Richardson P, Chauhan D, and Anderson KC. Ex vivo induction of multiple myeloma-specific cytotoxic T lymphocytes. Blood, 2003;102(4):1435-42.
Kohrgruber N, Haianek N, Groger M, Winter D, Rappersberg K, Schmitt-Egenolf M, Stingel G & Mauer D. Survival, maturation, and function of CD11c- and CD11c+ peripheral blood dendritic cells are differentially regulated by cytokines. Journal of Immunology, 1999;163:3250-3259.
Macatonia SE, Hosken NA, Litton M, Vieira P, Hsieh CS, Culpepper JA, Wysocka M, Trinchieri G, Murphy KM & O`Garra A. Dendritic cells produce IL-12 and direct the development of Th1 cells from naïve CD4+ T cells. Journal of Immunology, 1995;154:5071-5079.
Pfeiffer S, Gooding RP, Apperley JF, Goldschmidt H, Samson D. Dendritic cells generated from the blood of patients with multiple myeloma are phenotypically and functionally identical to those similarly produced from healthy donors. Br J Haematol., 1997;98(4):973-82.
Raje N, Gong J, Chauhan D, Teoh G, Avigan D, Wu Z, Chen D, Treon SP, Webb IJ, Kufe DW, Anderson KC. Bone marrow and peripheral blood dendritic cells from patients with multiple myeloma are phenotypically and functionally normal despite the detection of Kaposi`s sarcoma herpesvirus gene sequences. Blood. 1999;93:1487-95.
Ratta M, Fagnoni F, Curti A, Vescovini R, Sansoni P, Oliviero B, Fogli M, Ferri E, Della Cuna GR, Tura S, Baccarani M, Lemoli RM. Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood, 2002;100(1):230-7.
Rissoan MC, Soumelis V, Kadowaki N, Grouard G, Briere F, de Waal Malefyt R. & Liu YJ. Reciprocal control of T helper cell and dendritic cell differentiation. Science, 1999;283:1183-1186.
Robinson SP, Patterson S, English N, Davies D, Knight SC & Reid CD. Human peripheral blood contains two distinct lineages of dendritic cells. European Journal of Immunology, 1999;29:2769-2778.
Shortman K & Caux C. Dendritic cell development: multiple pathways to nature`s adjuvants. Stem Cells, 1997;15:409-419.
Tarte K, Lu ZY, Fiol G, Legouffe E, Rossi JF, Klein B. Generation of virtually pure and potentially proliferating dendritic cells from non-CD34 apheresis cells from patients with multiple myeloma. Blood, 1997;90(9):3482-95.
Xie J, Wang Y, Freeman ME 3rd, Barlogie B, Yi Q.Beta 2-microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells. Blood. 2003 May 15;101(10):4005-12.
Email this article (Login required) 
