Zagury J F, Sill A, Blattner W, Lachgar A, Le Buanec H, Richardson M, Rappaport J, Hendel H, Bizzini B, Gringeri A, Carcagno M, Criscuolo M, Burny A, Gallo R C, Zagury D
Université Pierre et Marie Curie, Paris, France.
J Hum Virol. 1998 May-Jun;1(4):282-92.
To investigate which immune parameters, such as antibodies against HIV-1 specificities, or viral parameters, such as p24 antigenemia, are predictive of disease progression.
We performed studies on serum collected from individuals exhibiting two extremes of disease evolution--67 fast progressors (FP) and 182 nonprogressors (NP)--at their enrollment. After a 1- to 2-year clinical follow-up of 104 nonprogressors after their enrollment, we could determine the best serologic predictors for disease progression.
We investigated levels of antibodies to tetanus toxoid and to HIV antigens including Env, Gag, Nef, and Tat proteins, as well as p24 antigenemia, viremia, CD4 cell count, and interferon-alpha (IFN-alpha) titers in FPs and NPs, and we correlated these data with clinical and biologic signs of progression.
p24 Antigenemia, a marker of viral replication, and anti-Tat antibodies were highly and inversely correlated in both groups (P < .001). Furthermore, anti-p24 antibodies and low serum IFN-alpha levels were correlated to the NP versus the FP cohort. Finally, among NPs, only antibodies to Tat and not to the other HIV specificities (Env, Nef, Gag) were significantly predictive of clinical stability during their follow-up.
Antibodies toward HIV-1 Tat, which are inversely correlated to p24 antigenemia, appear as a critical marker for a lack of disease progression. This study strongly suggests that rising anti-Tat antibodies through active immunization may be beneficial in AIDS vaccine development to control viral replication.
研究哪些免疫参数，如针对HIV-1特异性的抗体，或病毒参数，如p24抗原血症，可预测疾病进展。
我们对在入组时表现出疾病进展两个极端情况的个体——67名快速进展者（FP）和182名非进展者（NP）——采集的血清进行了研究。在104名非进展者入组后进行了1至2年的临床随访后，我们能够确定疾病进展的最佳血清学预测指标。
我们调查了FP组和NP组中破伤风类毒素抗体以及针对HIV抗原（包括Env、Gag、Nef和Tat蛋白）的抗体水平，以及p24抗原血症、病毒血症、CD4细胞计数和干扰素-α（IFN-α）滴度，并将这些数据与疾病进展的临床和生物学指标进行关联。
p24抗原血症（一种病毒复制标志物）与抗Tat抗体在两组中均呈高度负相关（P <.001）。此外，抗p24抗体和低血清IFN-α水平与NP组和FP组相关。最后，在NP组中，只有针对Tat的抗体而非针对其他HIV特异性（Env、Nef、Gag）的抗体在随访期间能显著预测临床稳定性。
与p24抗原血症呈负相关的针对HIV-1 Tat的抗体似乎是疾病无进展的关键标志物。这项研究强烈表明，通过主动免疫提高抗Tat抗体水平可能对艾滋病疫苗开发控制病毒复制有益。
