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

目的探讨HIV/AIDS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/AIDS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(×106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)×106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/AIDS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200×106个/L可能预示着机体更为严重的免疫损伤。

Characteristics of immunophenotypic alterations in 263 HIV/AIDS patients

OBJECTIVE: To explore the characteristics of immunophenotypic alterations of HIV-infected persons/AIDS patients--people living with AIDS (PLWA). METHODS: The clinical data and anti-coagulated 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), na?ve subset (CD4(+)CD45RA(+)CD62L(+) cell), and memory subset (CD4(+)CD45RA(-)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, na?ve CD4(+) T cell percentage, and CD28 expression rate in CD4(+) T cells of the PLWA were 205 (348, 63) x 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) x 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 x 10(6) cells/L, Group B with the CD4(+) T cell count of 200 - 350 x 10(6) cells/L, and Group C with the CD4(+) T cell count > 350 x 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 x 10(6) cells/L may predict more severe immunodeficiency.