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长期抗逆转录病毒治疗的艾滋病患者免疫功能重建研究

发布时间:2018-09-09 20:43
【摘要】:[目的]:研究艾滋病患者长期的有效抗逆转录病毒治疗后出现不同免疫学应答的特征,并进一步探讨艾滋病免疫功能重建的机制。 [方法]:从2002年10月至2013年9月于北京协和医院艾滋病诊疗中心规律随诊的患者31例,这些患者规律随诊,经抗病毒治疗8年以上,自基线、3月、6月、12月、18月、24月、30月、36月、42月、48月、54月、60月、66月、72月、78月、84月、90月、96月规律随访,检测血浆病毒载量、并采用流式细胞术技术检测外周血B淋巴细胞(CD19+)、NK淋巴细胞(CD16+CD56+)、CD4/CD8+T淋巴细胞(CD3+CD4+、CD3+CD8+)、纯真CD4+T淋巴细胞(CD4+CD45RA+CD62L+)、记忆CD4+T淋巴细胞(CD4+CD45RA-RO+)、CD8+T淋巴细胞激活亚群(CD8+CD38+/CD8、CD8+HLA-DR+/CD8+)、CD4/CD8+T淋巴细胞功能亚群(CD4+CD28+/CD4+、CD8+CD28+/CD8+)、CD4/CD8。对31例患者根据基线CD4+T淋巴细胞数值分组,A组(22例):基线CD4+T淋巴细胞200cells/mm3,B组(12例):200cells/mm3基线CD4+T淋巴细胞350cells/mm3,评价两组艾滋病患者在T淋巴细胞亚群的差异。 [结果l: 1.31例患者中,和健康对照组相比,NK淋巴细胞、CD4+T淋巴细胞、纯真CD4+T细胞、记忆CD4+T细胞绝对值、CD4/CD8显著降低(p0.05);记忆CD4+T细胞绝对值百分比、CD8+T淋巴细胞、CD8+HLA-DR+T淋巴细胞显著增高(p0.05); CD8+CD38+T淋巴细胞在治疗前2年显著高于健康对照组,而治疗第2年至第6年与健康对照组相似,而治疗第6年至治疗第8年显著低于健康对照组。 2.31例患者中,13例患者(41.9%)在治疗第8年时CD4+T淋巴细胞500/μl。 3.抗逆转录病毒治疗后免疫细胞亚群重建呈两个时相变化。我们发现,纯真CD4+T淋巴细胞在抗病毒治疗4年后增长速率较前4年显著减低(p0.05)。而CD8+CD38+T淋巴细胞百分比在抗病毒治疗4年后下降速率较前4年显著减低(p0.05)。 4.多因素分析中发现,男性、年龄大、临床存在艾滋病相关症状、基线CD4+T淋巴细胞200/μL、基线HIV病毒载量低、抗逆转录病毒治疗时间短是CD4+T淋巴细胞增加少的影响因素(p0.05)。 5.和基线CD4+T淋巴细胞200/μL组患者相比,基线CD4+T淋巴细胞200/μL组患者存在较高的CD8+T淋巴细胞和记忆CD4+T淋巴细胞百分比;存在较低的CD4+T细胞和纯真CD4+T细胞(p0.05)。 6、多因素分析中发现,女性、纯真CD4+T细胞百分比高是在抗逆转录病毒治疗第8年时CD4500/μL的影响因素(p0.05)。纯真CD4%在12.4%作为cut-off值,可预测晚期艾滋病病毒完全抑制的患者在抗逆转录病毒治疗第8年时CD4500/μL,敏感性为84.6%,特异性为88.2%。 [结论]: 1.艾滋病患者长期抗病毒治疗后仍存在部分免疫重建不全。 2.CD4+T细胞基线低时,存在较低的CD4+T细胞和纯真CD4+T细胞。这也支持早期开始抗逆转录病毒治疗。 3.纯真CD4%在12.4%作为cut-off值,可预测晚期艾滋病病毒完全抑制的患者在抗逆转录病毒治疗第8年时CD4500/μL
[Abstract]:Objective: to study the characteristics of different immunological responses after long term effective antiretroviral therapy in AIDS patients, and to explore the mechanism of AIDS immune function reconstruction. [methods]: from October 2002 to September 2013, 31 patients who were followed up regularly by AIDS diagnosis and treatment center of Peking Union Hospital were followed up regularly and treated with antiviral therapy for more than 8 years. From baseline, March, June, December, 18, 24, 30, 36, 42, 4, 54, 60, 66, 72, 7, 8, 84, 90, 9 months, followed up regularly to detect plasma viral load. Flow cytometry was used to detect CD4% CD8 T lymphocytes (CD3 CD4 CD3 CD8), CD4 T lymphocytes (CD4 CD45RA CD62L) and memory CD4 T lymphocytes (CD4 CD45RA-RO) activated CD8 T lymphocytes in peripheral blood B lymphocytes (CD19) and NK lymphocytes (CD16 CD56). CD8 CD38 / CD8 / CD8 HLA-DR / CD8 / CD4 CD28 / CD4 / CD8 / CD28 / CD8 / CD4 / CD8. Thirty-one patients were divided into two groups according to baseline CD4 T lymphocyte values: group A (22 cases): group B (12 cases) with baseline CD4 T lymphocytes 200cells / mm3 baseline CD4 T lymphocytes 350 cells / mm3 (n = 12). The difference of T lymphocyte subsets between the two groups was evaluated. [results: 1.The absolute value of CD _ 4 / CD _ 8 in NK lymphocytes, pure CD4 T cells and memory CD4 T cells was significantly lower than that in the control group (p0.05). The absolute percentage of memory CD4 T cells was significantly increased in CD8 T lymphocytes (p0.05), CD8 CD38 T lymphocytes were significantly higher than those in healthy control group 2 years before treatment, but similar to those in healthy control group from the 2nd to 6th year after treatment. From the 6th year to the 8th year, the CD4 T lymphocytes in 13 patients (41.9%) were significantly lower than those in the healthy control group (P < 0.05). After antiretrovirals treatment, the immune cell subsets were reconstructed in two phases. We found that the growth rate of pure CD4 T lymphocytes after 4 years of antiviral therapy was significantly lower than that of the previous 4 years (p0. 05). The percentage of CD8 CD38 T lymphocytes decreased significantly after 4 years of antiviral therapy (p0.05). Multivariate analysis showed that male, aged, had clinical AIDS-related symptoms, baseline CD4 T lymphocytes were 200 / 渭 L, and baseline HIV virus load was low. The short time of antiretrovirals therapy was the influence factor of CD4 T lymphocyte increase (p0. 05). The percentage of CD8 T lymphocytes and memory CD4 T lymphocytes in baseline CD4 T lymphocytes 200 / 渭 L group was higher than that in baseline CD4 T lymphocytes 200 / 渭 L group. There were low CD4 T cells and pure CD4 T cells (p0.05). Multivariate analysis showed that the high percentage of pure CD4 T cells in women was the influencing factor of CD4500/ 渭 L during the 8th year of antiretroviral therapy (p0.05). Pure CD4% was taken as cut-off value in 12.4%, which could predict CD4500/ 渭 L in the patients with complete inhibition of HIV in advanced stage. The sensitivity was 84.6% and the specificity was 88.2g / L in the 8th year of antiretrovirus therapy. [conclusion]: 1. After long term antiviral therapy, partial immunoreconstitution was still present in AIDS patients. When the baseline of 2.CD4 T cells was low, there were low CD4 T cells and pure CD4 T cells. This also supports the early start of antiretroviral therapy. Pure CD4% is 12. 4% as cut-off value, which can predict CD4500/ 渭 L in patients with complete suppression of HIV in the 8th year of antiretroviral therapy.
【学位授予单位】:北京协和医学院
【学位级别】:博士
【学位授予年份】:2014
【分类号】:R512.91

【参考文献】

相关期刊论文 前1条

1 ;Reference ranges and age-related changes of peripheral blood lymphocyte subsets in Chinese healthy adults[J];Science in China(Series C:Life Sciences);2009年07期



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