血清25-羟基维生素D3和外周血淋巴细胞维生素D受体水平与初诊成年人原发免疫性血小板减少症发病的相关性研究

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目的:探讨血清25-羟基维生素D3[25(OH)D3]和外周血淋巴细胞维生素D受体(VDR)水平,与初诊成年人原发免疫性血小板减少症(ITP)发病的相关性。方法:采取回顾性病例对照研究方法,选择2019年1月至12月于河北北方学院附属第一医院血液科门诊及住院部收治的55例初诊ITP成年患者为研究对象,并纳入ITP组(n n=55)。患者年龄为(42.6±11.8)岁;男性患者为19例,女性为36例。根据治疗效果将其分为完全反应(CR)、有效和无效3个亚组。并且选择同期于我院体检中心参加体检的性别、年龄匹配的30例健康体检者纳入健康对照组(n n=30)。对所有ITP患者采取初始治疗方案,对血小板计数<30×10n 9/L伴出血者加用联合治疗方案。使用酶联免疫吸附试验(ELISA)法检测ITP组患者治疗前、后和健康对照组受试者体检当日的血清25(OH)D3和外周血淋巴细胞VDR水平,并分析ITP组患者治疗前上述指标与其ITP相关实验室检查结果之间的关系。ITP组与健康对照组组间及ITP组组内治疗前、后血清25(OH)D3和外周血淋巴细胞VDR水平的比较,分别采用独立样本和配对样本n t检验,3个亚组间上述指标比较,采用方差分析。ITP组患者血清25(OH)D3、外周血淋巴细胞VDR水平与其ITP相关实验室检查结果的相关性分析,采用Pearson相关性分析。本研究经本院医学伦理委员会批准(批准文号:k2020060),所有受试对象均签署临床研究知情同意书。n 结果:① ITP组55例患者接受治疗2个月后,其疗效评估系CR、有效及无效者分别为28、12和15例,并将其分别纳入CR亚组(n n=28)、有效亚组(n n=12)和无效亚组(n n=15)。ITP组患者总有效率为72.7%(40/55)。② ITP组患者治疗前,血清25(OH)D3水平为(10.3± 3.8)ng/mL,显著低于健康对照组的(15.5±5.3) ng/mL,外周血淋巴细胞VDR水平为(219.6±79.4) nmol/L,显著高于后者的(159.8±52.3)nmol/L,并且差异均有统计学意义(n t=5.254、3.702, n P<0.001、<0.001)。治疗后,2组受试者血清25(OH)D3[(13.2±4.7)ng/mL比(15.5±5.3)ng/mL]和外周血淋巴细胞VDR水平[(187.6±63.7)nmol/L比(159.8±52.3) nmol/L]分别比较,差异均有统计学意义(n t=2.096、2.038, n P=0.039、0.045)。ITP组患者治疗前、后,血清25(OH)D3和外周血淋巴细胞VDR水平分别比较,差异均有统计学意义(n t=3.541、2.332,n P=0.001、0.022)。③ CR、有效和无效亚组患者治疗前血清25(OH)D3和外周血淋巴细胞VDR水平分别比较,差异均无统计学意义(n F=2.682、1.140,n P=0.078、0.327);3个亚组治疗后上述2个指标分别进行总体比较,差异均有统计学意义(n F=5.157、4.458,n P=0.009、0.016)。其中,CR亚组治疗后血清25(OH)D3和外周血淋巴细胞VDR水平分别与治疗前比较,差异均有统计学意义(n t=2.432、2.077,n P=0.018、0.043)。④治疗前,ITP组患者血清25(OH)D3水平与其血清C反应蛋白(CRP)、血小板表面相关免疫球蛋白(Ig)M(PAIgM)、血小板表面相关IgG(PAIgG)和血小板表面相关补体C3(PAC3)水平,均呈显著负相关关系(n r=-0.527、-0.319、-0.436、-0.347,n P=0.006、0.015、0.008、0.009),与其血小板计数呈正相关关系(n r=0.778、n P=0.001);外周血淋巴细胞VDR水平则与其上述4个指标呈显著正相关关系(n r=0.415、0.279、0.352、0.308,n P=0.008、0.029、0.011、0.017),与其血小板计数则呈负相关关系(n r=-0.639、n P=0.002)。⑤治疗前,ITP组患者血清25(OH)D3水平与其外周血淋巴细胞VDR水平呈显著负相关关系(n r=-0.983、n P<0.001)。n 结论:25(OH)D3缺乏与初诊成年人ITP的发病相关,血清25(OH)D3水平及外周血淋巴细胞VDR水平的异常可能参与初诊成年人ITP的发生、发展。补充维生素D3及其类似物可能是成年人ITP的新治疗方法。“,”Objective:To investigate the relationship between serum 25 hydroxyvitamin D3[25 (OH) D3] and vitamin D receptor (VDR) levels in peripheral blood lymphocytes and the onset of newly diagnosed primary immune thrombocytopenia (ITP) in adults.Methods:From January 2019 to December 2019, a total of 55 adults with newly diagnosed ITP in department of Hematology Department of First Affiliated Hospital of Hebei North University were involved in the study and set as ITP group (n n=55). The age of them was (42.6±11.8) years old, and there were 19 male patients and 36 females.Then they were further divided into complete response (CR) subgroup, effective subgroup and invalid subgroup according to their treatment effect. Meanwhile, a total of 30 health volunteers matched by gender and age who took part in physical examination in the physical examination center of our hospital in the same period were selected as the health control group (n n=30). The initial treatment plan was adopted for all patients, and the combined treatment plan was added to the patients with platelet count <30×10 n 9/L and bleeding symptoms.The levels of serum 25 (OH) D3 and VDR in peripheral blood lymphocytes were measured by enzyme-linked immunosorbent assay (ELISA), and the correlation between them and laboratory test indexes related ITP were analyzed.The comparison of serum 25(OH)D3 and peripheral blood lymphocyte VDR levels between ITP and health control groups and between before and after treatment within ITP group were performed by independent and paired sample n t-test.Variance analysis was used to compare the above indicators among three subgroups. The correlation analysis between serum 25(OH)D3 and peripheral blood lymphocytes VDR levels of patients in the ITP group and their laboratory test results before treatment was performed by Pearson correlation analysis.n Results:①After 2 months of treatment, among 55 patients in the ITP group, there were 28 CR, 12 effective, and 15 ineffective patients. They were included in the CR subgroup (n n=28), effective subgroup (n n=12) and invalid subgroup (n n=15), respectively. The total effective rate of patients in the ITP group was 72.7% (40/55). ② Before treatment, the level of serum 25 (OH) D3 in ITP group was (10.28±3.76) ng/mL, which was lower than that of (15.49±5.32) ng/mL in health control group, meanwhile the level of peripheral blood lymphocytes VDR in ITP group [(219.60±79.43)nmol/L] was higher than that of health control group [(159.84±52.27) nmol/L], and the differences were significant(n t=5.254, 3.702; n P<0.001, <0.001). After treatment, there were no significant differences between ITP group and health control group in level of serum 25 (OH) D3 [(13.2±4.7)ng/mLn vs (15.5±5.3) ng/mL] and peripheral blood lymphocytes VDR [(187.6±63.7)nmol/L n vs (159.8±52.3) nmol/L](n t=2.096, 2.038; n P=0.039, 0.045). In ITP group, there were significant differences before and after treatment(n t=3.541, 2.332; n P=0.001, 0.022). ③ There were no significant differences among CR subgroup, effective subgroup and invalid subgroup in levels of serum 25 (OH) D3 and peripheral blood lymphocytes VDR before treatment(n F=2.682, 1.140; n P=0.078, 0.327), and there were significant differences among them after treatment (n F=5.157, 4.458; n P=0.009, 0.016). In CR subgroup, the differences in levels of serum 25 (OH) D3 and peripheral blood lymphocytes VDR were statistically significant before and after treatment(n t=2.432, 2.077; n P=0.018, 0.043). ④ The level of serum 25(OH)D3 in the ITP group before treatment had significant negative correlation with their serum C-reactive protein (CRP), platelet surface-associated immunoglobulin (Ig) M (PAIgM), platelet surface-associated IgG (PAIgG) and platelet surface-associated complement C3 ( PAC3) level (n r=—0.527, -0.319, -0.436, -0.347; n P=0.006, 0.015, 0.008, 0.009), which was positively correlated with platelet count (n r=0.778, n P=0.001). In ITP group, the level of peripheral blood lymphocytes VDR was significantly positively correlated with serum CRP, PAIgM, PAIgG and PAC3 levels (n r=0.415, 0.279, 0.352, 0.308; n P=0.008, 0.029, 0.011, 0.017), negatively correlated with platelet count (n r=—0.639, n P=0.002). ⑤ The serum 25(OH)D3 level before treatment in the ITP group was significantly negatively correlated with the level of peripheral blood lymphocytes VDR (n r=—0.983, n P<0.001).n Conclusions:The deficiency of 25 (OH) D3 is related to the onset of ITP in newly diagnosed adults. The abnormal levels of serum 25 (OH) D3 and peripheral blood lymphocytes VDR may be involved in the occurrence and development of ITP in newly diagnosed adults.Vitamin D3 supplementation and its analogues may be a new target for ITP treatment in adults.
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