263例人类免疫缺陷病毒感染者/艾滋病患者免疫病理改变特点研究

Characteristics of immunophenotypic alterations in 263 HIV/AIDS patients

目的 探讨HIV／MDS患者免疫病理改变特点及其临床意义。方法收集北京协和医院诊治的263例未经抗病毒治疗的HIV／MDS患者临床资料，采集抗凝血标本经流式细胞仪检测淋巴细胞亚群，包括：B和NK细胞亚群，CD4^＋T和CD8^＋T细胞亚群，CD4^＋T细胞的功能亚群（CD28^＋CD4^＋），CD4^＋T细胞的纯真（CD4^＋CD45RA^＋CD62L^＋）和记忆（CD4^＋CD45RA^＋）亚群，CD8^＋T细胞的激活亚群（CD8^＋CD38^＋）；采用分支DNA（branch DNA，bDNA）法检测血浆病毒载量。并依据CD4^＋T细胞计数（×10^6个／L）小于200、200～350之间及大于350将病例分为A、B、C3组，比较组间差异。结果263例HIV／AIDS患者CD4^＋T细胞计数及其纯真亚群比例中位数（上、下四分位数）分别为205（348，63）×10^6个／L和18．5（32．0，6．5）％，显著低于正常对照组（P〈0．01）；CD4^＋T细胞功能亚群比例86．1（94.0，68．3）％，明显减低（P〈0．01）；CD4^＋T细胞计数与其CD28分子表达比例呈正相关（r=0．480，P〈0．01）；CD8^＋T细胞激活亚群比例达到84．3（92．7，69．0）％，显著高于正常对照组（P〈0．01），而且与血浆病毒载量呈正相关（r=0．331，P〈0．01）。据CD4^＋T细胞计数分组后比较显示：A组的病毒载量、CD8^＋T细胞激活亚群比例及记忆CD4^＋T细胞比例均显著高于B组和C组（P〈0．01），而纯真CD4^＋T细胞比例、CD4^＋T细胞功能亚群比例则显著低于B、C两组（P〈0．01）；B、C两组在CD4^＋T功能亚群比例、纯真及记忆CD4^＋T比例及CD8^＋T细胞激活亚群比例上均未见显著差异。结论中国HIV／MDS患者的免疫病理改变主要为CD4^＋T细胞及其纯真亚群数量减少，CD28表达比例减低和细胞免疫异常激活。本研究发现在不同疾病进展阶段存在不同的免疫病理改变特点，CD4^＋T细胞数低于200×10^6个／L可能预示着机体更为严重的免疫损伤。

Objective To explore the characteristics of immunophonotypic alterations of HIV-infected persons/AIDS patients-people living with AIDS （PLWA）, Methods The clinical data and anticoagulated blood samples of 263 treatment naive PLWA and 56 healthy controls were collected. Flow cytometry was used to determine the sets of peripheral lymphocytes： B cell, NK cell, CD4^＋ T cell including the functional subset（ CD28^＋ CD4^＋ cell）, naive subset（ CD4^＋ CD45RA^＋ CD62L^＋ cell）, and memory subset （ CD4^＋ CD45 RA^-cell） of CD4^＋ T cell, CD8^＋ T cell including the activated subset （ CD8 ^＋ CD38^＋ cell）. Branch DNA（bDNA） assay was used to detect the plasma viral load. Results The mean CD4^＋ T cell count, naive CD4^ ＋ T cell percentage, and CD28 expression rate in CD4^＋ T cells of the PLWA were 205 （348,63） ×10^6 cells/L, 18.5 （ 32.0, 6.5 ） %, and 86.1 （ 94. 0, 68.3 ） % respectively, all significantly lower than those of the healthy controls [ 787 （ 1058, 615 ）×10^6 cells/L, 35.4 （45.5, 30.0） %, and 95.7 （97.6, 91.0） % respectively, all P 〈 0. 01 ]. The percentage of CD38 expression in CD8^＋ T cells of the PLWA was 84.3（92.7, 69.0） %, significantly higher than that of the controls [42.6（50.6, 36.1 ） %, P 〈 0.01 ]. In the PLWA the CD4^＋T cell count was positively correlated with its CD28 expression （r = 0. 480, P 〈 0. 01 ）, and the percentage of CD38 expression in CD8^＋ T cells was positively correlated with eh plasma viral load（r = 0. 331, P 〈 0.01 ）. The PLWA were divided into 3 groups according to the CD4^＋ T cell count： Group A with the he CD4^＋T cell count 〈200×10^6 cells/L, Group B with the CD4＋^T cell count of 200-350×10^6 cells/L , and Group C with the CD4 ^＋ T cell count 〉 350×10^6 cells/L. In comparison with Groups B and C the plasma viral load, activated CD8^＋T cell subset proportion, and percentage of memory CD4^＋ T cells of Group A were all significantly higher, and the naive CD4^＋ T cell percentage and CD28 expression rate were both significantly lower（ all P 〈 0.01 ）. There were no significant differences in the percentage of memory CD4^＋ T cells, CD28 expression, and CD8^＋ T cell activated subset proportion between Groups B and C. Conclusion The major immunophenotypic alternations in the PLWA in China include significantly lower counts of CD4^＋ T cells and their naive subsets, marked down-regulation of CD28 expression and extremely activated CD8^＋ T cells. Distinct features of the immunophenotypic alteration may exist in different disease stages. The CD4^＋T cell count 〈 200×10^6 cells/L may predict more severe immunodeficiency.