Liu Yubin, Li Xiuxia, Han Yang, Qiu Zhifeng, Song Xiaojing, Li Bingxiang, Zhang Han, Wang Hongye, Feng Kai, Liu Longding, Wang Jingjing, Sun Ming, Li Taisheng
Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Institute of Medical Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming, China.
Front Med (Lausanne). 2020 Jul 17;7:299. doi: 10.3389/fmed.2020.00299. eCollection 2020.
B-cell-activating factor (BAFF) has been determined to be involved in HIV-1 infection and is correlated with disease progression, while its homologous molecule, a proliferation-inducing ligand (APRIL), is less frequently reported, and its role remains unclear. We aimed to characterize the APRIL levels in subjects with different HIV-1 infection statuses and determine the relationships with disease progression and immune activation. The plasma levels of APRIL were compared among 17 long-term non-progressors (LTNPs), 17 typical progressors (TPs), 10 ART-treated patients, and 10 healthy donors (HDs). Seventeen LTNPs and a subset of TPs ( = 6) who initiated ART were assessed longitudinally. The correlations between the APRIL levels and markers of disease progression, B-cell count and specific antibody response, and markers of immune activation and functional cells were analyzed. The circulating APRIL levels were significantly elevated in the LTNPs relative to the TPs, ART-treated patients, and HDs. The longitudinal investigation revealed that the APRIL levels were decreased during follow-up in the LTNPs. ART did not significantly influence the APRIL levels. The levels of plasma APRIL were negatively correlated with the plasma HIV-1 viral load and cellular HIV-1 DNA levels and positively correlated with the CD4 T-cell count and CD4/CD8 ratio. An inverse correlation was observed between the APRIL and BAFF levels. Furthermore, the APRIL levels were negatively correlated with the frequency of activated CD8 T cells and levels of interferon gamma-induced protein 10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1). Finally, positive correlations were observed among the APRIL levels, the frequency of CD8CD28 T cells, and natural killer (NK) cell count. The APRIL levels were elevated in the LTNPs and negatively correlated with disease progression and immune activation, suggesting likely protective activity in HIV-1 infection.
已确定B细胞激活因子（BAFF）参与HIV-1感染并与疾病进展相关，而其同源分子增殖诱导配体（APRIL）的报道较少，其作用仍不明确。我们旨在描述不同HIV-1感染状态受试者的APRIL水平，并确定其与疾病进展和免疫激活的关系。比较了17例长期不进展者（LTNP）、17例典型进展者（TP）、10例接受抗逆转录病毒治疗（ART）的患者和10例健康供者（HD）的血浆APRIL水平。对17例LTNP和一部分开始接受ART的TP（n = 6）进行了纵向评估。分析了APRIL水平与疾病进展标志物、B细胞计数和特异性抗体反应以及免疫激活和功能细胞标志物之间的相关性。与TP、接受ART治疗的患者和HD相比，LTNP的循环APRIL水平显著升高。纵向研究显示，LTNP在随访期间APRIL水平下降。ART对APRIL水平没有显著影响。血浆APRIL水平与血浆HIV-1病毒载量和细胞HIV-1 DNA水平呈负相关，与CD4 T细胞计数和CD4/CD8比值呈正相关。观察到APRIL和BAFF水平呈负相关。此外，APRIL水平与活化CD8 T细胞频率、干扰素γ诱导蛋白10（IP-10）和单核细胞趋化蛋白-1（MCP-1）水平呈负相关。最后，观察到APRIL水平、CD8CD28 T细胞频率和自然杀伤（NK）细胞计数之间呈正相关。LTNP的APRIL水平升高，且与疾病进展和免疫激活呈负相关，提示其在HIV-1感染中可能具有保护作用。
