HIV-1感染过程中血清趋化因子水平的纵向分析。

Longitudinal analysis of serum chemokine levels in the course of HIV-1 infection.

作者信息

Polo S, Veglia F, Malnati M S, Gobbi C, Farci P, Raiteri R, Sinicco A, Lusso P

机构信息

Unit of Human Virology, DIBIT, San Raffaele Scientific Institute, Milan, Italy.

出版信息

AIDS. 1999 Mar 11;13(4):447-54. doi: 10.1097/00002030-199903110-00002.

DOI:10.1097/00002030-199903110-00002

PMID:10197372

Abstract

OBJECTIVES

To investigate the correlation between the serum levels of the CC-chemokines RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, and the progression of HIV-1 disease.

DESIGN

Retrospective analysis of serial serum samples from HIV-1 seroconverters selected according to clinical outcome.

METHODS

Twenty-one patients, derived from a cohort recruited between 1985 and 1996 for a prospective study of the natural history of HIV infection, were analysed. All patients had at least one HIV-1-seronegative sample within 1 year prior to the first seropositive test and were followed longitudinally throughout the course of HIV-1 infection (mean follow-up, 73.5 months). Nine were rapid progressors (RP; patients who developed AIDS within 60 months of antibody seroconversion), seven were slow progressors (SP; patients who developed AIDS after 60 months), and five were long-term asymptomatic (LTA; patients with circulating CD4+ cells higher than 400 x 10(6)/l, no signs of HIV disease, no antiretroviral therapy for more than 96 months). A total of 339 serum samples was studied (mean, 16.1 per patient). The levels of RANTES, MIP-1alpha and MIP-1beta were measured by enzyme-linked immunosorbent assay and correlated with different immunological and clinical parameters.

RESULTS

Over the entire follow-up period, the geometric mean of serum RANTES was significantly higher in RP [68.6 ng/ml; 95% confidence interval (CI), 56.9-82.7] than in SP (23.7 ng/ml; 95% CI, 20.0-28.2; P < 0.001) and LTA (19.5 ng/ml; 95% CI, 15.5-24.5; P < 0.001). This difference was already significant during the early clinical stages, when patients had peripheral blood CD4+ cell counts still greater than 400 x 10(6)/l (P < 0.001). By contrast, the mean serum levels of MIP-1alpha and MIP-1beta did not differ significantly between the three study groups. Multivariate analysis using the Cox proportional hazard model demonstrated that the mean serum concentration of RANTES before the development of AIDS was independently associated with the time to AIDS (relative risk, 4.5; 95% CI, 1.1-18.2; P = 0.035). In patients with low versus high mean serum RANTES before the fall of CD4+ cells below 400 x 10(6)/l, the median AIDS-free time was 117.5 and 42.7 months, respectively (P = 0.037).

CONCLUSION

These data suggest that an elevation of serum RANTES predicts a rapid progression of the disease since the early stages of HIV-1 infection.

摘要

目的

研究CC趋化因子调节正常T细胞表达和分泌的趋化因子（RANTES）、巨噬细胞炎性蛋白（MIP）-1α和MIP-1β的血清水平与HIV-1疾病进展之间的相关性。

设计

对根据临床结局选择的HIV-1血清转化者的系列血清样本进行回顾性分析。

方法

分析了21例患者，这些患者来自1985年至1996年招募的一个队列，该队列用于对HIV感染的自然史进行前瞻性研究。所有患者在首次血清学阳性检测前1年内至少有一份HIV-1血清阴性样本，并在HIV-1感染过程中进行纵向随访（平均随访73.5个月）。9例为快速进展者（RP；抗体血清转化后60个月内发展为艾滋病的患者），7例为缓慢进展者（SP；60个月后发展为艾滋病的患者），5例为长期无症状者（LTA；循环CD4+细胞高于400×10⁶/l、无HIV疾病迹象、超过96个月未接受抗逆转录病毒治疗的患者）。共研究了339份血清样本（平均每位患者16.1份）。通过酶联免疫吸附测定法测量RANTES、MIP-1α和MIP-1β的水平，并将其与不同的免疫和临床参数相关联。

结果

在整个随访期间，RP组血清RANTES的几何平均值[68.6 ng/ml；95%置信区间（CI），56.9 - 82.7]显著高于SP组（23.7 ng/ml；95% CI，20.0 - 28.2；P < 0.001）和LTA组（19.5 ng/ml；95% CI，15.5 - 24.5；P < 0.001）。在临床早期阶段，当患者外周血CD4+细胞计数仍大于400×10⁶/l时，这种差异就已经很显著（P < 0.001）。相比之下，三个研究组之间MIP-1α和MIP-1β的平均血清水平没有显著差异。使用Cox比例风险模型进行的多变量分析表明，艾滋病发生前RANTES的平均血清浓度与艾滋病发生时间独立相关（相对风险，4.5；95% CI，1.1 - 18.2；P = 0.035）。在CD4+细胞降至400×10⁶/l以下之前，血清RANTES平均水平低与高的患者中，无艾滋病的中位时间分别为117.5个月和42.7个月（P = 0.037）。