INMI L. Spallanzani IRCCS, Rome, Italy.
Blood Transfusion Center, Legnano General Hospital, Legnano, Italy.
PLoS One. 2019 Dec 23;14(12):e0225415. doi: 10.1371/journal.pone.0225415. eCollection 2019.
A significant proportion of HIV-infected patients experiencing a late diagnosis highlights the need to define immunological protocols able to help the clinicians in identifying patients at higher risk for immunological failure. The aim of the study was to evaluate the feasibility of easy cytometric tests in defining the effect of antiretroviral treatment (cART) on immunological homeostasis and in identifying predictive markers of early immune recovery. Chronic HIV infected patients (n = 202) were enrolled in a prospective multicentric study, and their immunological profile was studied before (w0) and after 24 weeks (w24) of antiretroviral treatment (cART) using a standardized flow cytometric panel. Based on CD4 T cell count before treatment, patients were divided in late (LP: CD4 <350/mmc), intermediate (IP: 350/mmc<CD4<500/mmc) and early (EP: CD4 >500/mmc) presenters. In all groups, cART introduction increased CD4 and CD4/CD8 T cell ratio, naïve T cell (CD4 and CD8) and CD127-expressing CD4 T cells. In parallel, cART significantly reduced effector memory T cells (CD4 and CD8) and T cell activation (CD38+CD8 and CD95+CD4 T cells). Moreover, the frequency of Naïve and Effector CD4 T cells before treatment correlated with several immune parameters key associated with the pathogenesis of HIV, thus mirroring the health of immune system. Interestingly, we identified the Naïve/Effector CD4 T cell ratio (N/EM) at w0 as a marker able to predict early immune recovery. Specifically, in LP, N/EM ratio was significantly higher in immunological responder patients (CD4>500/mmc at w24) when compared to immunological non responder (CD4 T cells <500/mmc at w24). Finally, a multivariate analysis indicates that after 24w patients with N/EM ratio higher than 1.86 at w0 recovered 96 CD4 T cells more than those with N/EM ratio lower than 0.46. Altogether, our data define an easy protocol able to define reliable immunological markers useful for the characterization of immune profile in viremic HIV patients and identify the naïve/effector CD4 T cell ratio as a new tool able to predict an early immune reconstitution potential.
相当比例的 HIV 感染者存在延迟诊断的情况，这突出表明有必要定义免疫方案，以帮助临床医生识别免疫功能失败风险更高的患者。本研究旨在评估易于进行的细胞计量学检测在确定抗逆转录病毒治疗 (cART) 对免疫稳态的影响以及识别早期免疫恢复预测标志物方面的可行性。202 例慢性 HIV 感染者纳入前瞻性多中心研究，在开始 cART 前（w0）和 24 周（w24）后，使用标准化流式细胞术面板研究其免疫谱。根据治疗前 CD4 T 细胞计数，将患者分为晚期（LP：CD4<350/mmc）、中期（IP：350/mmc<CD4<500/mmc）和早期（EP：CD4>500/mmc）患者。在所有组中，cART 引入均增加了 CD4 和 CD4/CD8 T 细胞比值、幼稚 T 细胞（CD4 和 CD8）和表达 CD127 的 CD4 T 细胞。同时，cART 显著减少了效应记忆 T 细胞（CD4 和 CD8）和 T 细胞活化（CD38+CD8 和 CD95+CD4 T 细胞）。此外，治疗前幼稚和效应 CD4 T 细胞的频率与与 HIV 发病机制密切相关的多个免疫参数相关，从而反映了免疫系统的健康状况。有趣的是，我们发现治疗前的幼稚/效应 CD4 T 细胞比值（N/EM）可以作为预测早期免疫恢复的标志物。具体来说，在 LP 中，与免疫无应答者（w24 时 CD4 T 细胞<500/mmc）相比，免疫应答者（w24 时 CD4>500/mmc）患者的 N/EM 比值显著更高。最后，多变量分析表明，在 24 周时，N/EM 比值高于 1.86 的患者比 N/EM 比值低于 0.46 的患者多恢复了 96 个 CD4 T 细胞。总之，我们的数据定义了一种简单的方案，能够确定可靠的免疫标志物，有助于描述病毒血症 HIV 患者的免疫谱，并将幼稚/效应 CD4 T 细胞比值确定为预测早期免疫重建潜力的新工具。
