Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
mBio. 2021 Mar 9;12(2):e00170-21. doi: 10.1128/mBio.00170-21.
Plasma viremia reoccurs in most HIV-infected individuals once antiretroviral therapy (ART) is interrupted. The kinetics of viral rebound, specifically the time until plasma virus becomes detectable, differ quite substantially between individuals, and associations with virological and immunological factors have been suggested. Standard clinical measures, like CD4 T-cell counts and plasma HIV RNA levels, however, are poor predictive markers. Antibody features, including Fc functionality and Fc glycosylation have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we analyzed HIV-specific antibody quantities and qualitative differences like antibody-mediated functions, Fc gamma receptor (FcγR) binding, and IgG Fc glycosylation as well as cytokine profiles and cellular HIV DNA and RNA levels in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders (≤4 weeks versus >4 weeks) and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. Specifically, individuals with early viral rebound exhibited higher levels of total HIV-specific IgGs carrying inflammatory Fc glycans, while delayed rebounders showed an enrichment of highly functional antibodies. Overall, only four features, including enhanced antibody-mediated NK cell activation in delayed rebounders, were necessary to discriminate the groups. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future ATI studies. Plasma viremia reoccurs in most HIV-infected individuals once antiretroviral therapy is interrupted, and interindividual differences in the kinetics of viral rebound have been associated with virological and immunological factors. Antibody features, including Fc functionality and Fc glycosylation, have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we systematically analyzed HIV-specific antibody quantities and qualitative differences in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future HIV eradication studies.
血浆病毒血症在大多数感染 HIV 的个体中会再次出现，一旦中断抗逆转录病毒治疗 (ART)。病毒反弹的动力学，特别是血浆病毒变得可检测到的时间，在个体之间有很大的不同，并且已经提出了与病毒学和免疫学因素的关联。然而，标准的临床措施，如 CD4 T 细胞计数和血浆 HIV RNA 水平，是预测标志物。抗体特征，包括 Fc 功能和 Fc 糖基化，已被确定为多种疾病中疾病活动的敏感替代物。在这里，我们分析了 23 名接受抗逆转录病毒治疗的个体在进行分析性抗逆转录病毒中断 (ATI) 之前的 HIV 特异性抗体数量和定性差异，如抗体介导的功能、FcγR（FcγR）结合和 IgG Fc 糖基化以及细胞因子谱和细胞 HIV DNA 和 RNA 水平。我们发现，具有不同功能特性和 Fc 聚糖特征的抗体将个体分为早期和延迟病毒反弹者（≤4 周与>4 周），并与炎症细胞因子水平和病毒库的转录活性相关。具体来说，早期病毒反弹的个体表现出携带炎症性 Fc 聚糖的总 HIV 特异性 IgG 水平较高，而延迟反弹者表现出高度功能性抗体的富集。总体而言，只有四个特征，包括延迟反弹者中增强的抗体介导的 NK 细胞激活，足以区分两组。这些数据表明，抗体特征可用作 HIV 疾病活动的敏感指标，并可纳入未来的 ATI 研究中。
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