【摘要】：[目的]：研究艾滋病患者長期的有效抗逆轉(zhuǎn)錄病毒治療后出現(xiàn)不同免疫學(xué)應(yīng)答的特征,并進(jìn)一步探討艾滋病免疫功能重建的機(jī)制。 [方法]：從2002年10月至2013年9月于北京協(xié)和醫(yī)院艾滋病診療中心規(guī)律隨診的患者31例,這些患者規(guī)律隨診,經(jīng)抗病毒治療8年以上,自基線、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月規(guī)律隨訪,檢測血漿病毒載量、并采用流式細(xì)胞術(shù)技術(shù)檢測外周血B淋巴細(xì)胞(CD19+)、NK淋巴細(xì)胞(CD16+CD56+)、CD4/CD8+T淋巴細(xì)胞(CD3+CD4+、CD3+CD8+)、純真CD4+T淋巴細(xì)胞(CD4+CD45RA+CD62L+)、記憶CD4+T淋巴細(xì)胞(CD4+CD45RA-RO+)、CD8+T淋巴細(xì)胞激活亞群(CD8+CD38+/CD8、CD8+HLA-DR+/CD8+)、CD4/CD8+T淋巴細(xì)胞功能亞群(CD4+CD28+/CD4+、CD8+CD28+/CD8+)、CD4/CD8。對31例患者根據(jù)基線CD4+T淋巴細(xì)胞數(shù)值分組,A組(22例)：基線CD4+T淋巴細(xì)胞200cells/mm3,B組(12例)：200cells/mm3基線CD4+T淋巴細(xì)胞350cells/mm3,評價(jià)兩組艾滋病患者在T淋巴細(xì)胞亞群的差異。 [結(jié)果l： 1.31例患者中,和健康對照組相比,NK淋巴細(xì)胞、CD4+T淋巴細(xì)胞、純真CD4+T細(xì)胞、記憶CD4+T細(xì)胞絕對值、CD4/CD8顯著降低(p0.05)；記憶CD4+T細(xì)胞絕對值百分比、CD8+T淋巴細(xì)胞、CD8+HLA-DR+T淋巴細(xì)胞顯著增高(p0.05); CD8+CD38+T淋巴細(xì)胞在治療前2年顯著高于健康對照組,而治療第2年至第6年與健康對照組相似,而治療第6年至治療第8年顯著低于健康對照組。 2.31例患者中,13例患者(41.9%)在治療第8年時(shí)CD4+T淋巴細(xì)胞500/μl。 3.抗逆轉(zhuǎn)錄病毒治療后免疫細(xì)胞亞群重建呈兩個時(shí)相變化。我們發(fā)現(xiàn),純真CD4+T淋巴細(xì)胞在抗病毒治療4年后增長速率較前4年顯著減低(p0.05)。而CD8+CD38+T淋巴細(xì)胞百分比在抗病毒治療4年后下降速率較前4年顯著減低(p0.05)。 4.多因素分析中發(fā)現(xiàn),男性、年齡大、臨床存在艾滋病相關(guān)癥狀、基線CD4+T淋巴細(xì)胞200/μL、基線HIV病毒載量低、抗逆轉(zhuǎn)錄病毒治療時(shí)間短是CD4+T淋巴細(xì)胞增加少的影響因素(p0.05)。 5.和基線CD4+T淋巴細(xì)胞200/μL組患者相比,基線CD4+T淋巴細(xì)胞200/μL組患者存在較高的CD8+T淋巴細(xì)胞和記憶CD4+T淋巴細(xì)胞百分比；存在較低的CD4+T細(xì)胞和純真CD4+T細(xì)胞(p0.05)。 6、多因素分析中發(fā)現(xiàn),女性、純真CD4+T細(xì)胞百分比高是在抗逆轉(zhuǎn)錄病毒治療第8年時(shí)CD4500/μL的影響因素(p0.05)。純真CD4%在12.4%作為cut-off值,可預(yù)測晚期艾滋病病毒完全抑制的患者在抗逆轉(zhuǎn)錄病毒治療第8年時(shí)CD4500/μL,敏感性為84.6%,特異性為88.2%。 [結(jié)論]： 1.艾滋病患者長期抗病毒治療后仍存在部分免疫重建不全。 2.CD4+T細(xì)胞基線低時(shí),存在較低的CD4+T細(xì)胞和純真CD4+T細(xì)胞。這也支持早期開始抗逆轉(zhuǎn)錄病毒治療。 3.純真CD4%在12.4%作為cut-off值,可預(yù)測晚期艾滋病病毒完全抑制的患者在抗逆轉(zhuǎn)錄病毒治療第8年時(shí)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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R512.91

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

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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本文編號：2233519