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Short Communication: Elevated Labile Iron Levels in CD4 and CD8 T Cells from HIV-Positive Individuals with Undetectable Viral Load.
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2020-07-02 , DOI: 10.1089/aid.2020.0010 Radoslava Emilova 1 , Victor Manolov 2 , Yana Todorova 1 , Nina Yancheva 3 , Ivailo Alexiev 4 , Maria Nikolova 1
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2020-07-02 , DOI: 10.1089/aid.2020.0010 Radoslava Emilova 1 , Victor Manolov 2 , Yana Todorova 1 , Nina Yancheva 3 , Ivailo Alexiev 4 , Maria Nikolova 1
Affiliation
Iron is a key factor at various stages of HIV life cycle and determines the progression of HIV infection. Data about cellular labile iron pool (LIP) in the settings of contemporary antiretroviral therapy (cART) are lacking. Yet LIP is directly related to the generation of reactive oxygen species, and may contribute to immune activation, dysfunction, and exhaustion. Using multiparameter flow cytometry, we evaluated LIP in CD4 and CD8 T cells from HIV+ patients with sustained viral suppression (SVS) as a result of continuous long-term cART. Based on the recovery of CD4/CD8 ratio, two patients' subgroups were defined: A (n = 26), CD4/CD8 > 0.9, and B (n = 37), CD4/CD8 < 0.9, with significantly differing CD4 absolute count (AC) (mean 752 vs. 571 cells/μL, p < .05). Although hemoglobin and serum iron had recovered in all patients, CD4 T cell LIP and CD8 T cell LIP were significantly higher than that of controls, both in the subgroup with complete (A) and with incomplete (B) immune recovery [mean CD4 mean fluorescence intensity (ΔMFI) 318.7 and 777.8 vs. 157.6; mean CD8 ΔMFI 359.5 and 628.7 vs. 179.2, analysis of variance p < .05 for both]. CD4 LIP correlated inversely with CD4 AC (R = −0.4, p < .01), and both CD4 LIP and CD8 LIP—with CD4/CD8 ratio (R = −0.4, p < .01). Thus, increased CD4 T cell LIP and CD8 T cell LIP in the settings of SVS and immune recovery are a sensitive marker of residual immune activation and may predict immune exhaustion in long-term cART-treated patients.
中文翻译:
简短交流:来自无法检测到病毒载量的HIV阳性个体的CD4和CD8 T细胞中不稳定铁水平升高。
铁是艾滋病毒生命周期各个阶段的关键因素,并决定了艾滋病毒感染的进程。缺乏有关当代抗逆转录病毒疗法(cART)情况下的细胞不稳定铁池(LIP)的数据。然而,LIP与活性氧的产生直接相关,并且可能导致免疫激活,功能障碍和衰竭。使用多参数流式细胞术,我们评估了由于持续长期cART而导致持续病毒抑制(SVS)的HIV +患者的CD4和CD8 T细胞中的LIP。根据CD4 / CD8比值的恢复,定义了两个患者亚组:A(n = 26),CD4 / CD8> 0.9,B(n = 37),CD4 / CD8 <0.9,CD4绝对计数显着不同(AC)(平均752 vs.571细胞/μL,p <.05)。尽管所有患者的血红蛋白和血清铁均已恢复,但在完全(A)和不完全(B)免疫恢复的亚组中,CD4T细胞LIP和CD8T细胞LIP均显着高于对照组[平均CD4平均荧光强度(ΔMFI)318.7和777.8与157.6;平均CD8ΔMFI分别为359.5和628.7与179.2, 两者的方差分析p <.05]。CD4 LIP与CD4 AC成反比(R = -0.4,p <.01),而CD4 LIP和CD8 LIP均与CD4 / CD8比成反比(R = -0.4,p <.01)。因此,在SVS和免疫恢复的情况下,CD4 T细胞LIP和CD8 T细胞LIP的增加是残余免疫激活的敏感标志,并可预测长期接受cART治疗的患者的免疫力衰竭。
更新日期:2020-07-03
中文翻译:
简短交流:来自无法检测到病毒载量的HIV阳性个体的CD4和CD8 T细胞中不稳定铁水平升高。
铁是艾滋病毒生命周期各个阶段的关键因素,并决定了艾滋病毒感染的进程。缺乏有关当代抗逆转录病毒疗法(cART)情况下的细胞不稳定铁池(LIP)的数据。然而,LIP与活性氧的产生直接相关,并且可能导致免疫激活,功能障碍和衰竭。使用多参数流式细胞术,我们评估了由于持续长期cART而导致持续病毒抑制(SVS)的HIV +患者的CD4和CD8 T细胞中的LIP。根据CD4 / CD8比值的恢复,定义了两个患者亚组:A(n = 26),CD4 / CD8> 0.9,B(n = 37),CD4 / CD8 <0.9,CD4绝对计数显着不同(AC)(平均752 vs.571细胞/μL,p <.05)。尽管所有患者的血红蛋白和血清铁均已恢复,但在完全(A)和不完全(B)免疫恢复的亚组中,CD4T细胞LIP和CD8T细胞LIP均显着高于对照组[平均CD4平均荧光强度(ΔMFI)318.7和777.8与157.6;平均CD8ΔMFI分别为359.5和628.7与179.2, 两者的方差分析p <.05]。CD4 LIP与CD4 AC成反比(R = -0.4,p <.01),而CD4 LIP和CD8 LIP均与CD4 / CD8比成反比(R = -0.4,p <.01)。因此,在SVS和免疫恢复的情况下,CD4 T细胞LIP和CD8 T细胞LIP的增加是残余免疫激活的敏感标志,并可预测长期接受cART治疗的患者的免疫力衰竭。