维持性血液透析乙型肝炎病毒感染患者淋巴细胞亚群变化与CKD-MBD的相关性研究

A Study on the relationship between the changes of lymphocyte subgroups and chronic kidney disease and mineral and bone disorder in maintenance hemodialysis patients with HBV infection

目的比较感染乙型肝炎病毒(hepatitis B virus,HBV)和未感染HBV的维持性血液透析(maintenance hemodialysis,MHD)患者淋巴细胞亚群百分比、矿物质与骨代谢水平及微炎症状态等指标的变化;观察HBV感染的MHD患者淋巴细胞亚群变化与慢性肾脏病-矿物质与骨代谢异常(chronic kidney disease-mineral and bone disorder,CKD-MBD)之间的相关性。方法接受血液透析(hemodialysis,HD)治疗3个月以上的终末期肾病患者62例,根据透析开始前是否合并HBV感染将患者分为2组:HD组33例,HBV-HD组29例。采用单克隆抗体流式细胞术检测淋巴细胞亚群百分比,放射性同位素法检测全段甲状旁腺素(intact parathyroid hormone,iPTH)水平,酶联免疫吸附法检测微炎症因子。结果在血常规检查中,16.13%(10/62)的患者观察到白细胞计数降低,升高5例,53.23%(33/62)的患者有淋巴细胞百分比降低,升高3例;与HD组相比,HBV-HD组的淋巴细胞百分比和绝对值显著降低(P<0.05),T淋巴细胞百分比显著下降(P<0.05),其中Th细胞百分比、CD4+/CD8+比值降低(P<0.05),Treg细胞百分比升高(P<0.01),Ts细胞百分比无明显差异(P>0.05);与HD组相比,HBV-HD组B淋巴细胞百分比差异无统计学意义(P>0.05),NK淋巴细胞百分比显著降低(P<0.05);与HD组相比,HBV-HD组的iPTH和钙磷乘积增高(P<0.05),C反应蛋白、TNF-α、IL-6水平增高(P<0.05),血钙、血磷、β2微球蛋白、骨碱性磷酸酶水平无明显差异(P>0.05)。相关分析显示,两组Th细胞百分比、CD4+/CD8+比值、NK淋巴细胞百分比与iPTH水平和钙磷乘积之间存在负相关性。结论MHD患者存在不同程度的淋巴细胞亚群数量减少,HBV感染后T淋巴细胞和NK淋巴细胞亚群数量减少程度加重,HBV感染患者更容易发生CKD-MBD,CKD-MBD可能参与了T淋巴细胞和NK淋巴细胞亚群免疫功能的抑制,由于免疫缺陷可诱发和加重感染,HBV感染的MHD患者微炎症状态更严重。

Objective To compare the changes of lymphocyte subgroup percentages,mineral and bone metabolism levels and microinflammation status in maintenance hemodialysis(MHD)patients with and without hepatitis B virus(HBV)infection,and to observe the correlation between lymphocyte subgroup changes and chronic kidney disease and mineral and bone disorder(CKD-MBD)in patients with HBV infection.Methods A total of 62 patients with end-stage renal disease who had been treated with MHD for more than 3 months were divided into two groups:HD group(33 cases)and HBV-HD group(29 cases).The percentage of lymphocyte subgroups was detected by monoclonal antibody flow cytometry,the level of parathyroid hormone(PTH)was detected by radioisotope method,and microinflammatory factors were detected by enzyme-linked immunosorbent assay.Results In routine blood examination,16.13%(10/62)patients were observed to show a decrease in white blood cell count with an increase in 5 cases,53.23%(33/62)patients had a decrease in lymphocyte percentage with an increase in 3 cases.Compared with the HD group,the percentage and absolute value of lymphocyte in the HBV-HD group were significantly decreased(P<0.05),and the percentage of T lymphocyte was significantly increased(P<0.05).The percentage of Th cells,and CD4+/CD8+ratio decreased(P<0.05),the percentage of Treg cells increased(P<0.01),and the change of Ts cells had no significant difference(P>0.05).Compared with the HD group,the percentage of B lymphocytes in the HBV-HD group had no significant difference(P>0.05),and the percentage of NK lymphocytes decreased significantly(P<0.05).Compared with the HD group,the level of PTH and calcium-phosphorus product increased in the HBV-HD group(P<0.05),the levels of C-reactive protein,TNF-αand IL-6 increased(P<0.05),while the levels of serum Ca,P,beta-2 microglobulin and bone alkaline phosphatase had no significant difference(P>0.05).The correlation analysis showed that there was a negative correlation between Th cell percentage,CD4+/CD8+ratio,NK lymphocyte percentage and the level of PTH and calcium-phosphorus product in the two groups.Conclusions In MHD patients,the number of lymphocyte subgroups decreases to different degrees,and the numbers of T lymphocyte and NK lymphocyte subgroups decrease to a greater extent after HBV infection.CKD-MBD is more likely to occur in patients with HBV infection.CKD-MBD may be involved in the suppression of immune function of T lymphocytes.Since immune deficiency can induce and aggravate infection,the microinflammation of MHD patients infected with HBV may be more serious.