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The Impact Of Bortezomib Therapy On DC Subsets, IL-6, TNF-α In Newly Diagnosed Multiple Myeloma Patients And The Correlational Study With β2-MG

Posted on:2017-03-29Degree:MasterType:Thesis
Country:ChinaCandidate:Y H MaFull Text:PDF
GTID:2284330503962097Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Objective:The purpose of this study was to detect the proportion of myeloid dendritic cells(m DC), plasmacytoid dendritic cells(p DC) and interleukin-6(IL-6), tumor necrosis factor-alpha(TNF-α) in peripheral blood sample from newly diagnosed multiple myeloma patients before and after bortezomib treatment. Then make comparisons between clinical prognostic indicators including β2-microglobulin(β2-MG) and the above change.Methods: Collected 21 cases of newly diagnosed multiple myeloma inpatient in Lanzhou University Second Hospital during December 2013 to December 2015. 11 normal individuals were enrolled in the study. All the clinic and laboratory data were collected among the MM who were diagnosed, used 1~2 courses of PAD therapy and the normal ones. The propotions of m DC, p DC in peripheral blood were measured by flow cytometry. The concentration of IL-6,TNF-α levels were detected using ELISA. Then make a correlation among the frequency of m DC,p DC, TNF-α, IL-6 and β2-MG.Results: 1. The proportion of m DC in peripheral blood of MM patients before treatment decreased significantly comparing with the normal controls(0.57±0.12% vs 1.06±0.10%, P <0.001), the proportion of p DC in MM patients before treatment was lower than that in the normal controls(0.17±0.11% vs 0.79±0.10%, P<0.001); The proportion of m DC in MM patients after treatment was higher than that in patients before treatment(0.98±0.15% vs 0.57±0.12%, P <0.001), the proportion of p DC in patients after treatment was higher comparing with patients before treatment(0.69±0.30 % vs 0.17±0.11%, P < 0.001); but no evident difference in m DC(0.98±0.15% vs 1.06±0.10%, P=0.050), p DC(0.69±0.30% vs 0.79±0.10%, P=0.138) was found between MM patients after treatment and the normal controls. The mean proportion of DC from peripheral blood of patients in stageⅠwas significantly higher in comparison with the corresponding cells of patients in stage Ⅲ, m DC(0.67±0.12% vs 0.52±0.10%, P<0.05), p DC(0.28±0.16% vs 0.11±0.04%, P<0.05). 2. The frequency of m DC and the serum concentration ofβ2-MG in patients after treatment was negatively correlated(r=﹣0.569, P<0.05). The frequency of p DC and the serum concentration of β2-MG in patients after treatment was negatively correlated(r=﹣0.693, P<0.05). The frequency of m DC in stage Ⅲ and the serum concentration of β2-MG in patients before treatment was negatively correlated(r= ﹣ 0.883, P < 0.05). The frequency of p DC in stage Ⅲ and the serum concentration of β2-MG in patients before treatment was negatively correlated(r=﹣0.881, P<0.05). 3. The level of IL-6 in peripheral blood of MM patients before treatment increased significantly comparing with the normal controls(13.78±7.08 vs 4.73±2.19, P<0.001), the level of TNF-α in peripheral blood of MM patients before treatment was higher than that in the normal controls(34.05±10.11 vs 14.98±7.57, P<0.001); The level of IL-6 in peripheral blood of MM patients after treatment was lower than that in patient before treatment(6.42±3.33 vs 13.78±7.08, P<0.001), the level of TNF-α in peripheral blood of MM patients after treatment was lower comparing with patient before treatment(18.72±5.43 vs34.05±10.11, P<0.001); but no evident difference in IL-6(6.42±3.33 vs 4.73±2.19, P=0.059),TNF-α(18.72±5.43 vs 14.98±7.57, P=0.090) was found between MM patients after treatment and the normal controls. A more pronounced increase in the level of IL-6, TNF-α was noted in the peripheral blood from patients with the most advanced disease, the differences reached statistical significance, when compared to earlier stages. The mean level of cytokines from peripheral blood of patients in stageⅠwas significantly lower in comparison with the corresponding cytokines of patients in stage Ⅱ, IL-6(7.20±3.84 vs 11.78±2.80, P<0.05, TNF-α(24.18±5.78 vs 32.92±5.86,P<0.05); The level of IL-6 in peripheral blood of MM patients in stage Ⅰ decreased significantly comparing with the stage Ⅲ(7.20±3.84 vs 19.69±5.97, P < 0.001), the level of TNF-α in peripheral blood of MM patients in stage Ⅰ was lower than that in stage Ⅲ(24.18±5.78 vs41.39±8.87, P<0.001); The level of IL-6 in stage Ⅱ of MM patients was lower than that in stageⅢ(11.78±2.80 vs 19.69±5.97, P<0.05), the level of TNF-α in stage Ⅱ of MM patients was lower than that in stage Ⅲ(32.92±5.86 vs 41.39±8.87, P<0.05). 4. The level of IL-6 and the serum concentration of β2-MG in patients before treatment was positively correlated(r=0.623, P<0.01).The level of TNF-α and the serum concentration of β2-MG in patients before treatment was positively correlated(r=0.769, P<0.01), the level of IL-6 and TNF-α in patients before treatment was positively correlated(r=0.515, P < 0.05).The level of IL-6 in stage Ⅲ and the serum concentration of β2-MG in patients before treatment was positively correlated(r=0.800, P<0.05).The level of TNF-α in stage Ⅲ and the serum concentration of β2-MG in patients before treatment was positively correlated(r=0.833, P<0.05).Conclusions:1. The proportion of DC subsets decreased in newly diagnosed MM patients,the frequency of m DC, p DC and the serum concentration of β2-MG was negatively correlated.Initial and secondary immunodeficiency may involved in the pathogenesis of MM. 2. The level of IL-6, TNF-α increased in MM patients which was positive correlated with the serum concentration of β2-MG,suggesting they were involved in the pathogenesis of MM. 3.In the patients who increased in stage, they had the lower proportion of DC subsets, the higher level of IL-6, TNF-α,the prognosis was worse. 4. Bortezomib therapy can increase the proportion of DC subsets, reduce the level of cytokine TNF-, IL-6.To a certain extent,Bortezomib can improve immune disorders of patients with MM.
Keywords/Search Tags:multiple myeloma, dendritic cells, interleukin-6, tumor necrosis factor-alpha, β2-microglobulin
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