Neutralizing antibodies are positively associated with CD4+ T-cell counts and T-cell function in long-term AIDS-free infection

Neutralizing antibodies are positively associated with CD4+ T-cell counts and T-cell function in long-term AIDS-free infection
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DOI:
10.1097/00002030-199813000-00005
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发表时间:
1998-09-10
期刊:
影响因子:
3.8
通讯作者:
Goudsmit, J
Goudsmit, J
中科院分区:
医学2区
文献类型:
--
作者:
Carotenuto, P;Looij, D;Goudsmit, J

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目的:为了评估动态的中和抗体(NAB)在长期无艾滋病的HIV-1感染的受试者,并建立相关性与已知的标志物的疾病progression.Design:横断面研究使用血清收集的长期非进展(LTNP)8年后血清转换或研究条目。纵向研究使用血清从LTNP收集在0,0.5,1,2,4,6,8和10年后血清转换,作为对照,从快速progressor.Methods:个人与记录的艾滋病免费HIV-1感染至少8年进行了评估NAB对五个异源HIV-1主要分离株。在横断面研究中,血清病毒RNA水平,CD 4 + T细胞数量和T细胞功能在第八年随访期间收集的样本进行了测定。对于纵向研究,在取自LTNP和快速进展者的连续血清中评估NAb。在单个血清中发现的血清中和滴度从一个HIV-1分离株到另一个分离株不同,在49-76%的LTNP中检测到,与分离株的辅助受体使用无关,与CD 4 + T淋巴细胞计数(P = 0.0041)和T细胞功能(P = 0.04)呈正相关。NAb与血清Vital RNA水平及CD_4 ~+ T细胞下降时间无相关性。对LTNP和快速进展者血清的纵向分析显示,尽管两组中的几个受试者在血清转换时具有中和活性,但此后中和活性降低或不再可检测。NAb在LTNP患者中1-4年后再次出现,并持续稳定存在,但在快速进展者中仍检测不到或处于低水平。在这些个体中,对异源分离株的中和活性随时间增加。这些数据表明,广泛产生NAb的能力是免疫系统完整性的函数。(C)1998年利平科特·威廉姆斯和威尔金斯。
Objectives: To assess the dynamics of neutralizing antibodies (NAb) in long-term AIDS-free HIV-1-infected subjects and establish correlations with known markers of disease progression.Design: Cross-sectional study using sera collected from long-term non-progressors (LTNP) 8 years after seroconversion or study entry. Longitudinal study using sera collected from LTNP at 0, 0.5, 1, 2, 4, 6, 8 and 10 years after seroconversion and, as controls, from rapid progressors.Methods: Individuals with documented AIDS-free HIV-1 infection for at least 8 years were evaluated for NAb against five heterologous HIV-1 primary isolates. In the cross-sectional study, serum viral RNA levels, CD4+ T-cell numbers and T-cell function were determined on samples collected during the eighth year of follow-up. For the longitudinal study, NAb were assessed in sequential sera taken From LTNP and rapid progressors.Results: Serum neutralization titres found in individual sera differed fi-om one HIV-1 isolate to another, were detected in 49-76% of LTNP, without correlation with the coreceptor usage of the isolate, and were positively associated with CD4+ T-lymphocyte counts (P = 0.0041) and T-cell function (P = 0.04). No correlation was found between NAb and the level of vital RNA in serum or the late of CD4+ T-cell decline. Longitudinal analysis of sera from LTNP and rapid progressors showed that although several subjects in both groups had neutralizing activity at seroconversion, it thereafter became lower or no longer detectable. NAb were again found 1-4 yeats later and stably persisted in LTNP, but remained undetectable or at low levels in rapid progressors.Conclusions: NAb were preferentially Found in subjects with relatively preserved T-cell function and CD4+ T-cell numbers. In these individuals, neutralizing activity against heterologous isolates increased with time. These data suggest that the capacity to produce broadly NAb is a function of the integrity of the immune system. (C) 1998 Lippincott Williams & Wilkins.