Perturbation of B Cell Gene Expression Persists in HIV-Infected Children Despite Effective Antiretroviral Therapy and Predicts H1N1 Response.
Perturbation of B Cell Gene Expression Persists in HIV-Infected Children Despite Effective Antiretroviral Therapy and Predicts H1N1 Response.
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DOI：
10.3389/fimmu.2017.01083
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发表时间：
2017
影响因子：
7.3
通讯作者：
Pahwa S
中科院分区：
文献类型：
--
作者：
Cotugno N;De Armas L;Pallikkuth S;Rinaldi S;Issac B;Cagigi A;Rossi P;Palma P;Pahwa S
尽管抗逆转录病毒治疗（ART）有效，但具有明显相似临床和免疫学特征的艾滋病毒感染者对疫苗接种的反应可能不同。然而，导致这种损伤的分子机制以及能够预测艾滋病毒感染儿童疫苗反应的生物标志物仍然未知。假设尽管有效的抗逆转录病毒治疗和表型B细胞免疫重建，但HIV感染儿童（HIV）的B细胞质量缺陷仍然存在，本研究的目的是研究与年龄匹配的健康对照（hc）相比，HIV的B细胞基因表达，并确定不同的基因表达模式是否可以预测对流感疫苗的反应能力。为此，我们使用多重RT-PCR分析了从外周血单个核细胞中分离的相同数量的排序纯化B细胞亚群（SPBS）中96个基因组的疫苗接种前转录水平。所有研究参与者接种三价灭活流感疫苗（TIV）后，通过血凝抑制和记忆B细胞ELISpot测定对H1N1抗原的免疫应答。尽管HIV和HC之间SPBS的细胞频率没有差异，但根据基因表达分析，这两组是可以区分的。事实上，与HC相比，尽管长期病毒控制（>24个月），在HIV激活记忆B细胞（CD27+CD21−）中观察到28个基因特征，其特征是参与炎症反应和免疫激活的基因表达更高。进一步的分析，考虑到HIV参与者在TIV后的H1N1应答，揭示了静息记忆（RM） B细胞（CD27+CD21+）中的25个基因标记能够区分疫苗应答者和无应答者（NR）。事实上，与NR相比，应答者的预防接种RM B细胞表现出更高的参与B细胞适应性免疫应答的基因集（APRIL， BTK, BLIMP1）和BCR信号（MTOR， FYN, CD86）的表达。总体而言，这些数据表明，尽管通过抗逆转录病毒治疗在hiv感染儿童中实现了稳定的病毒控制，但B细胞区室转录水平的扰动仍然存在。此外，本研究表明，在接种疫苗前对RM B细胞进行转录评估，以确定该人群中疫苗反应的预测性相关因素，具有潜在的实用性。
Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine. To do so, we analyzed prevaccination transcriptional levels of a 96-gene panel in equal numbers of sort-purified B cell subsets (SPBS) isolated from peripheral blood mononuclear cells using multiplexed RT-PCR. Immune responses to H1N1 antigen were determined by hemaglutination inhibition and memory B cell ELISpot assays following trivalent-inactivated influenza vaccination (TIV) for all study participants. Although there were no differences in terms of cell frequencies of SPBS between HIV and HC, the groups were distinguishable based upon gene expression analyses. Indeed, a 28-gene signature, characterized by higher expression of genes involved in the inflammatory response and immune activation was observed in activated memory B cells (CD27+CD21−) from HIV when compared to HC despite long-term viral control (>24 months). Further analysis, taking into account H1N1 responses after TIV in HIV participants, revealed that a 25-gene signature in resting memory (RM) B cells (CD27+CD21+) was able to distinguish vaccine responders from non-responders (NR). In fact, prevaccination RM B cells of responders showed a higher expression of gene sets involved in B cell adaptive immune responses (APRIL, BTK, BLIMP1) and BCR signaling (MTOR, FYN, CD86) when compared to NR. Overall, these data suggest that a perturbation at a transcriptional level in the B cell compartment persists despite stable virus control achieved through ART in HIV-infected children. Additionally, the present study demonstrates the potential utility of transcriptional evaluation of RM B cells before vaccination for identifying predictive correlates of vaccine responses in this population.
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DOI：
10.1084/jem.20130323
发表时间：
2013-11-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Deenick EK;Avery DT;Chan A;Berglund LJ;Ives ML;Moens L;Stoddard JL;Bustamante J;Boisson-Dupuis S;Tsumura M;Kobayashi M;Arkwright PD;Averbuch D;Engelhard D;Roesler J;Peake J;Wong M;Adelstein S;Choo S;Smart JM;French MA;Fulcher DA;Cook MC;Picard C;Durandy A;Klein C;Holland SM;Uzel G;Casanova JL;Ma CS;Tangye SG
通讯作者：
Tangye SG
影响因子：
5.5
作者：
Hu, Zhiliang;Luo, Zhenwu;Wan, Zhuang;Wu, Hao;Li, Wei;Zhang, Tong;Jiang, Wei
通讯作者：
Jiang, Wei
影响因子：
4.6
作者：
Bamford A;Hart M;Lyall H;Goldblatt D;Kelleher P;Kampmann B
通讯作者：
Kampmann B
影响因子：
5.5
作者：
Cagigi, Alberto;Pensieroso, Simone;Chiodi, Francesca
通讯作者：
Chiodi, Francesca
DOI：
10.1073/pnas.1621489114
发表时间：
2017-02-28
影响因子：
11.1
作者：
Kazmin, Dmitri;Nakaya, Helder I.;Pulendran, Bali
通讯作者：
Pulendran, Bali