系统性红斑狼疮患者血清25-羟维生素D水平与淋巴细胞亚群的关系
发布时间：2018-07-22 20:31
【摘要】：目的:系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种以免疫性炎症为突出表现的自身免疫性疾病。目前认为SLE发病与环境、遗传、激素水平及免疫异常等因素相关,但具体机制尚未完全阐明。SLE患者体内除产生大量自身抗体外,还存在免疫细胞、细胞因子等免疫异常。维生素D作为一种神经-内分泌-免疫调节激素,通过与特定的维生素D受体(vitamin D receptor,VDR)结合,对抗原呈递细胞、T细胞、B细胞等免疫细胞发挥效应,调节免疫细胞的增殖与分化、炎症因子及免疫球蛋白表达等。据报道维生素D不足与多种自身免疫性疾病相关,如多发性硬化(multiplesclerosis,MS)、Ⅰ型糖尿病(type 1 diabetes mellitus,T1DM)、炎性肠病(Inflammatory Bowel Disease,IBD)、类风湿关节炎(rheumatoid arthritis,RA)、SLE等。SLE患者普遍存在维生素D水平减低和淋巴细胞亚群异常。本研究通过检测初发SLE患者及健康人的血清25(OH)D3及外周血淋巴细胞亚群,分析SLE患者25(OH)D3水平和淋巴细胞亚群的情况,并探讨25(OH)D3与淋巴细胞亚群的关系、临床意义和两者在SLE发病机制中的作用。方法:采用化学发光微粒子免疫检测法检测31例初发系统性红斑狼疮患者血清25-羟维生素D水平与21例健康对照组进行比较。采用流式细胞术检测31例初发系统性红斑狼疮患者外周血CD3+T细胞、CD3+CD4+Th细胞、CD3+CD8+Ts细胞、Th/Ts、CD19+B细胞及CD3-CD16+56+NK细胞百分率并与健康对照组进行比较。对系统性红斑狼疮患者25-羟维生素D水平与系统性红斑狼疮疾病活动指数(systemic lupus erythematosus disease activity index,SLEDAI)、淋巴细胞亚群进行相关分析。结果:1 25(OH)D3在SLE组的水平低于对照组[(10.19±3.94)ng/ml]与[(14.11±3.62)ng/ml](t=-3.63,P0.05);2依据SLEDAI评分进行分组,在非活动组25(OH)D3水平与对照组无显著差异[(12.46±3.25)ng/ml]与[(14.11±3.62)ng/ml](t=-1.50,P0.05),活动组低于非活动组[(7.05±2.39)ng/ml]与[(12.46±3.25)ng/ml](t=5.08,P0.05),活动组低于对照组[(7.05±2.39)ng/ml]与[(14.11±3.62)ng/ml](t=-6.22,P0.05);3 SLE患者外周血CD3+T细胞百分率与对照组之间差异无统计学意义[(69.54±8.73)%]与[(71.31±6.33)%](t=-0.80,P0.05),SLE患者CD3+CD4+Th细胞百分率[(28.48±8.13)%]低于对照组[(40.64±5.04)%],差异有统计学意义(t=-6.10,P0.05)。SLE患者Th/Ts[0.80(0.50,1.03)]低于对照组[1.50(1.20,1.79)],差异有统计学意义(Z=-4.9,P0.05)。SLE患者CD3-CD16+56+NK细胞百分率[(5.77±3.17)%]低于对照组[(12.20±2.50)%],差异有统计学意义(t=-7.80,P0.05)。SLE患者CD3+CD8+Ts细胞百分率[(38.61±10.07)%]高于对照组[(28.62±4.51%)],差异有统计学意义(t=4.85,P0.05)。SLE患者CD19+B细胞[(19.70±7.90)%]高于对照组[(11.01±3.81)%],差异有统计学意义(t=5.28,P0.05);4非活动组CD3+T细胞百分率[(71.82±7.85)%]与对照组[(71.31±6.33)%]之间差异无统计学意义(t=0.23,P0.05),非活动组CD3+CD4+Th细胞百分率[(33.45±6.44)%]低于对照组[(40.65±5.04)%](t=-3.91,P0.05),非活动组Th/Ts[1.01(0.75,1.18)]低于对照组[1.50(1.20,1.79)](Z=-3.73,P0.05),非活动组CD3-CD16+56+NK细胞百分率[(5.07±2.89)%]低于对照组[(12.20±2.50)%](t=-8.26,P0.05),CD3+CD8+Ts细胞、CD19+B细胞百分率高于对照组[(35.12±8.02)%]与[(28.62±4.51)%](t=3.05,P0.05)和[(17.19±6.76)%]与[(11.01±3.81)%](t=3.58,P0.05);5活动组CD3+T细胞百分率与对照组之间差异无统计学意义[(66.39±9.21)%]与[(71.31±6.33)%](t=-1.85,P0.05),活动组CD3+CD4+Th细胞百分率[(21.59±4.26)%]低于对照组[(40.64±5.04)%](t=-3.91,P0.05),活动组Th/Ts[0.49(0.39,0.70)]低于对照组[1.50(1.20,1.79)](Z=-4.63,P0.05),活动组CD3-CD16+56+NK细胞百分率[(6.74±3.38)%]低于对照组[(12.20±2.50)%](t=-5.40,P0.05);CD3+CD8+Ts细胞、CD19+B细胞百分率高于对照组[(43.44±10.91)%]与[(28.62±4.51)%](t=4.66,P0.05)和[(23.17±8.29)%]与[(11.01±3.81)%)](t=4.97,P0.05);6活动组与非活动组CD3+T细胞百分率[(66.39±9.21)%]与[(71.82±7.85)%](t=1.77,P0.05)、CD3-CD16+56+NK细胞百分率[(6.74±3.38)%]与[(5.07±2.89)%](t=-1.48,P0.05)之间差异均无统计学意义,活动组CD3+CD4+Th细胞百分率、Th/Ts均低于非活动组[(21.59±4.26)%]与[(33.45±6.44)%](t=5.77,P0.05)、[0.49(0.39,0.70)]与[1.01(0.75,1.18)](Z=-3.39,P0.05),CD3+CD8+Ts细胞和CD19+B细胞百分率均高于非活动组[(43.44±10.91)%]与[(35.12±8.02)%](t=-2.45,P0.05)、[(23.17±8.29)%]与[(17.19±6.76)%](t=-2.21,P0.05);7 SLE患者按Th/Ts比值分为两组,倒置组25(OH)D3水平低于未倒置组[(9.07±3.94)ng/ml]与[(11.95±3.40)ng/ml](t=-2.09,P0.05);8 SLE组25(OH)D3水平与SLEDAI呈负相关(r=-0.545,P0.05),SLE组25(OH)D3水平与CD3+CD4+Th细胞百分率、Th/Ts正相关(r=0.456,P0.05)、(r=0.477,P0.05)。SLE组25(OH)D3水平与CD3+T细胞、CD3+CD8+Ts细胞、CD19+B细胞、CD3-CD16+56+NK细胞百分率均无相关性(P0.05)。结论:1 SLE患者存在25(OH)D3水平降低及淋巴细胞亚群异常,并可作为SLE患者疾病活动的一项参考指标。2 SLE患者血清25(OH)D3水平与淋巴细胞亚群CD3+CD4+Th细胞百分率、Th/Ts负相关,维生素D可能与SLE发病有关。
[Abstract]:Objective: systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune inflammation. At present, it is believed that the pathogenesis of SLE is related to environment, heredity, hormone level and immune abnormality, but the specific mechanism has not yet fully demonstrated that there is still a large number of autoantibodies in the body of.SLE patients. Immune cells, cytokines, and other immune abnormalities. Vitamin D, as a neuroendocrine immunomodulatory hormone, is combined with a specific vitamin D receptor (vitamin D receptor, VDR) to antagonism immune cells, such as primary presenting cells, T cells, B cells, and other immune cells, regulating the proliferation and differentiation of immune cells, inflammatory factors and immunoglobulin It is reported that vitamin D deficiency is associated with a variety of autoimmune diseases, such as multiple sclerosis (multiplesclerosis, MS), type I diabetes (type 1 diabetes mellitus, T1DM), inflammatory bowel disease (Inflammatory Bowel Disease, IBD), rheumatoid arthritis (rheumatoid), and so on. This study analyzed the level of 25 (OH) D3 and lymphocyte subsets in patients with primary SLE and healthy human serum 25 (OH) D3 and peripheral blood lymphocyte subsets, and explored the relationship between 25 (OH) D3 and lymphocyte subsets, the clinical significance and the role of the two in the pathogenesis of SLE. The serum 25- hydroxyvitamin D levels of 31 patients with primary systemic lupus erythematosus were compared with that of 21 healthy controls. Flow cytometry was used to detect the peripheral blood CD3+T cells, CD3+CD4+Th cells, CD3+CD8 +Ts cells, Th/Ts, CD19+B cells and CD3-CD16+56+NK fine of 31 patients with primary systemic lupus erythematosus. The percentage of 25- hydroxyvitamin D in systemic lupus erythematosus patients and systemic lupus erythematosus disease activity index (systemic lupus erythematosus disease activity index, SLEDAI) and lymphocyte subsets were analyzed. Results: 125 (OH) D3 in the SLE group was lower than that of the control group [(10.19 + 3.) 94) ng/ml] and [(14.11 + 3.62) ng/ml] (t=-3.63, P0.05); 2 on the basis of SLEDAI score, there was no significant difference between the non active group 25 (OH) D3 and the control group [12.46 + 3.25) ng/ml] and [(14.11 + 3.62) ng/ml] (t=-1.50, P0.05), and the active group was lower than the non active group [7.05 + 2.39) ng/ml] and [12.46 + 3.25). (7.05 + 2.39) ng/ml] and [(14.11 + 3.62) ng/ml] (t=-6.22, P0.05); the percentage of CD3+T cells in peripheral blood of patients with 3 SLE was not statistically significant [(69.54 + 8.73)%] and [(71.31 + 6.33)%] (t=-0.80, P0.05), and the percentage of CD3+CD4+Th cells in SLE patients [(28.48 + 8.13)%] was lower than that of the control group [(40.64 + 5.04)%], the difference was statistically significant The meaning (t=-6.10, P0.05).SLE patients Th/Ts[0.80 (0.50,1.03)] was lower than the control group [1.50 (1.20,1.79)], the difference was statistically significant (Z=-4.9, P0.05).SLE patients CD3-CD16+56+NK cell percentage [(5.77 + 3.17)%] was lower than the control group [(12.20 + 2.50)%], the difference was (38.61 + 10.07) (38.61 + 10.07). Higher than the control group [(28.62 + 4.51%)], the difference was statistically significant ((t=4.85, P0.05).SLE patients CD19+B cells [(19.70 + 7.90)%] higher than the control group [(11.01 + 3.81)%], the difference was statistically significant (t=5.28, P0.05); 4 non active group CD3+T cell percentage [(71.82 + 7.85)%] and the control group [(71.31 + 6.33)%] difference was not statistically significant (t=0.23, P0.) 05) the percentage of CD3+CD4+Th cells in the inactive group [(33.45 + 6.44)%] was lower than that of the control group [(40.65 + 5.04)%] (t=-3.91, P0.05), the non active group Th/Ts[1.01 (0.75,1.18)] was lower than the control group [1.50 (1.20,1.79)] (Z=-3.73, P0.05), the percentage of the non active group CD3-CD16+56+NK cells [(5.07 + 2.89)%] was lower than that of the control group [(12.20 + 2.50)%] (t=-8.26, P0.05). The percentage of CD19+B cells was higher than that in the control group [(35.12 + 8.02)%] and [(28.62 + 4.51)%] (t=3.05, P0.05) and [(17.19 + 6.76)%] and [(11.01 + 3.81)%] (t=3.58, P0.05), and there was no statistical difference between the percentage of CD3+T cells in the active group and the control group [(66.39 + 9.21)%] and [(71.31 + 6.33)%] (t=-1.85, P0.05), and the percentage of CD3+CD4+Th cells in the active group. The rate [(21.59 + 4.26)%] was lower than that of the control group [(40.64 + 5.04)%] (t=-3.91, P0.05), Th/Ts[0.49 (0.39,0.70) in the active group was lower than the control group [1.50 (1.20,1.79)] (Z=-4.63, P0.05). The percentage of CD3-CD16+56+NK cells in the active group [(6.74 + 3.38)%] was lower than that of the control group [(12.20 + 2.50)%] (t=-5.40, P0.05), and the percentage of CD3+CD8+Ts cells was higher than that of the control group. (43.44 + 10.91)%] and [(28.62 + 4.51)%] (t=4.66, P0.05) and [(23.17 + 8.29)%] and [(11.01 + 3.81)%]] (t=4.97, P0.05); the percentage of CD3+T cells in the 6 active group and the inactive group [(66.39 + 9.21)%] and [(71.82 + 7.85)%] (t=1.77, P0.05), the percentage of CD3-CD16+ 56+NK cells [(6.74 +]%)] and [(t=-1.48, P0.05)] have no statistics The percentage of CD3+CD4+Th cells in the active group was lower than that in the non active group [(21.59 + 4.26)%] and [(33.45 + 6.44)%] (t=5.77, P0.05), [0.49 (0.39,0.70)] and [1.01 (0.75,1.18)] (Z=-3.39, P0.05), and the percentage of CD3+CD8+Ts cells and CD19+B cells were higher than those in the non active group [(43.44 + 10.91)%] and [35.12 + 8.02)%], [23.17 + 8.2]. 9)%] and [(17.19 + 6.76)%] (t=-2.21, P0.05); 7 SLE patients were divided into two groups according to the ratio of Th/Ts, and the level of 25 (OH) D3 in the inverted group was lower than that in the non inverted Group [9.07 + 3.94) ng/ml] and [11.95 + 3.40) ng/ml] (t=-2.09, P0.05), and the level of 25 (OH) was positively correlated with the percentage of cells. (r=0.456, P0.05), (r=0.477, P0.05).SLE group 25 (OH) D3 levels have no correlation with CD3+T cells, CD3+CD8+Ts cells, CD19+B cells, and CD3-CD16+56+NK cells (P0.05). Conclusion: there is a decrease in the level of 25 (1) and the abnormal lymphocyte subgroup, and can be used as a reference index for the disease activity of the patients. The level of D3 is negatively correlated with the percentage of CD3+CD4+Th lymphocyte and Th/Ts, and vitamin D may be related to the pathogenesis of SLE.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R593.241
本文编号：2138485
[Abstract]:Objective: systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune inflammation. At present, it is believed that the pathogenesis of SLE is related to environment, heredity, hormone level and immune abnormality, but the specific mechanism has not yet fully demonstrated that there is still a large number of autoantibodies in the body of.SLE patients. Immune cells, cytokines, and other immune abnormalities. Vitamin D, as a neuroendocrine immunomodulatory hormone, is combined with a specific vitamin D receptor (vitamin D receptor, VDR) to antagonism immune cells, such as primary presenting cells, T cells, B cells, and other immune cells, regulating the proliferation and differentiation of immune cells, inflammatory factors and immunoglobulin It is reported that vitamin D deficiency is associated with a variety of autoimmune diseases, such as multiple sclerosis (multiplesclerosis, MS), type I diabetes (type 1 diabetes mellitus, T1DM), inflammatory bowel disease (Inflammatory Bowel Disease, IBD), rheumatoid arthritis (rheumatoid), and so on. This study analyzed the level of 25 (OH) D3 and lymphocyte subsets in patients with primary SLE and healthy human serum 25 (OH) D3 and peripheral blood lymphocyte subsets, and explored the relationship between 25 (OH) D3 and lymphocyte subsets, the clinical significance and the role of the two in the pathogenesis of SLE. The serum 25- hydroxyvitamin D levels of 31 patients with primary systemic lupus erythematosus were compared with that of 21 healthy controls. Flow cytometry was used to detect the peripheral blood CD3+T cells, CD3+CD4+Th cells, CD3+CD8 +Ts cells, Th/Ts, CD19+B cells and CD3-CD16+56+NK fine of 31 patients with primary systemic lupus erythematosus. The percentage of 25- hydroxyvitamin D in systemic lupus erythematosus patients and systemic lupus erythematosus disease activity index (systemic lupus erythematosus disease activity index, SLEDAI) and lymphocyte subsets were analyzed. Results: 125 (OH) D3 in the SLE group was lower than that of the control group [(10.19 + 3.) 94) ng/ml] and [(14.11 + 3.62) ng/ml] (t=-3.63, P0.05); 2 on the basis of SLEDAI score, there was no significant difference between the non active group 25 (OH) D3 and the control group [12.46 + 3.25) ng/ml] and [(14.11 + 3.62) ng/ml] (t=-1.50, P0.05), and the active group was lower than the non active group [7.05 + 2.39) ng/ml] and [12.46 + 3.25). (7.05 + 2.39) ng/ml] and [(14.11 + 3.62) ng/ml] (t=-6.22, P0.05); the percentage of CD3+T cells in peripheral blood of patients with 3 SLE was not statistically significant [(69.54 + 8.73)%] and [(71.31 + 6.33)%] (t=-0.80, P0.05), and the percentage of CD3+CD4+Th cells in SLE patients [(28.48 + 8.13)%] was lower than that of the control group [(40.64 + 5.04)%], the difference was statistically significant The meaning (t=-6.10, P0.05).SLE patients Th/Ts[0.80 (0.50,1.03)] was lower than the control group [1.50 (1.20,1.79)], the difference was statistically significant (Z=-4.9, P0.05).SLE patients CD3-CD16+56+NK cell percentage [(5.77 + 3.17)%] was lower than the control group [(12.20 + 2.50)%], the difference was (38.61 + 10.07) (38.61 + 10.07). Higher than the control group [(28.62 + 4.51%)], the difference was statistically significant ((t=4.85, P0.05).SLE patients CD19+B cells [(19.70 + 7.90)%] higher than the control group [(11.01 + 3.81)%], the difference was statistically significant (t=5.28, P0.05); 4 non active group CD3+T cell percentage [(71.82 + 7.85)%] and the control group [(71.31 + 6.33)%] difference was not statistically significant (t=0.23, P0.) 05) the percentage of CD3+CD4+Th cells in the inactive group [(33.45 + 6.44)%] was lower than that of the control group [(40.65 + 5.04)%] (t=-3.91, P0.05), the non active group Th/Ts[1.01 (0.75,1.18)] was lower than the control group [1.50 (1.20,1.79)] (Z=-3.73, P0.05), the percentage of the non active group CD3-CD16+56+NK cells [(5.07 + 2.89)%] was lower than that of the control group [(12.20 + 2.50)%] (t=-8.26, P0.05). The percentage of CD19+B cells was higher than that in the control group [(35.12 + 8.02)%] and [(28.62 + 4.51)%] (t=3.05, P0.05) and [(17.19 + 6.76)%] and [(11.01 + 3.81)%] (t=3.58, P0.05), and there was no statistical difference between the percentage of CD3+T cells in the active group and the control group [(66.39 + 9.21)%] and [(71.31 + 6.33)%] (t=-1.85, P0.05), and the percentage of CD3+CD4+Th cells in the active group. The rate [(21.59 + 4.26)%] was lower than that of the control group [(40.64 + 5.04)%] (t=-3.91, P0.05), Th/Ts[0.49 (0.39,0.70) in the active group was lower than the control group [1.50 (1.20,1.79)] (Z=-4.63, P0.05). The percentage of CD3-CD16+56+NK cells in the active group [(6.74 + 3.38)%] was lower than that of the control group [(12.20 + 2.50)%] (t=-5.40, P0.05), and the percentage of CD3+CD8+Ts cells was higher than that of the control group. (43.44 + 10.91)%] and [(28.62 + 4.51)%] (t=4.66, P0.05) and [(23.17 + 8.29)%] and [(11.01 + 3.81)%]] (t=4.97, P0.05); the percentage of CD3+T cells in the 6 active group and the inactive group [(66.39 + 9.21)%] and [(71.82 + 7.85)%] (t=1.77, P0.05), the percentage of CD3-CD16+ 56+NK cells [(6.74 +]%)] and [(t=-1.48, P0.05)] have no statistics The percentage of CD3+CD4+Th cells in the active group was lower than that in the non active group [(21.59 + 4.26)%] and [(33.45 + 6.44)%] (t=5.77, P0.05), [0.49 (0.39,0.70)] and [1.01 (0.75,1.18)] (Z=-3.39, P0.05), and the percentage of CD3+CD8+Ts cells and CD19+B cells were higher than those in the non active group [(43.44 + 10.91)%] and [35.12 + 8.02)%], [23.17 + 8.2]. 9)%] and [(17.19 + 6.76)%] (t=-2.21, P0.05); 7 SLE patients were divided into two groups according to the ratio of Th/Ts, and the level of 25 (OH) D3 in the inverted group was lower than that in the non inverted Group [9.07 + 3.94) ng/ml] and [11.95 + 3.40) ng/ml] (t=-2.09, P0.05), and the level of 25 (OH) was positively correlated with the percentage of cells. (r=0.456, P0.05), (r=0.477, P0.05).SLE group 25 (OH) D3 levels have no correlation with CD3+T cells, CD3+CD8+Ts cells, CD19+B cells, and CD3-CD16+56+NK cells (P0.05). Conclusion: there is a decrease in the level of 25 (1) and the abnormal lymphocyte subgroup, and can be used as a reference index for the disease activity of the patients. The level of D3 is negatively correlated with the percentage of CD3+CD4+Th lymphocyte and Th/Ts, and vitamin D may be related to the pathogenesis of SLE.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R593.241
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