High APRIL Levels Are Associated With Slow Disease Progression and Low Immune Activation in Chronic HIV-1-Infected Patients

Yubin Liu; Xiuxia Li; Yang Han; Zhifeng Qiu; Xiaojing Song; Bingxiang Li; Han Zhang; Hongye Wang; Kai Feng; Longding Liu; Jingjing Wang; Ming Sun; Taisheng Li

doi:10.3389/fmed.2020.00299

High APRIL Levels Are Associated With Slow Disease Progression and Low Immune Activation in Chronic HIV-1-Infected Patients

Front Med (Lausanne). 2020 Jul 17:7:299. doi: 10.3389/fmed.2020.00299. eCollection 2020.

Authors

Yubin Liu¹, Xiuxia Li¹, Yang Han¹, Zhifeng Qiu¹, Xiaojing Song¹, Bingxiang Li^{2

3}, Han Zhang^{2

3}, Hongye Wang^{2

3}, Kai Feng^{2

3}, Longding Liu^{2

3}, Jingjing Wang^{2

3}, Ming Sun^{2

3}, Taisheng Li^{1

4

5}

Affiliations

¹ Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
² Institute of Medical Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming, China.
³ Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming, China.
⁴ Clinical Immunology Center, Chinese Academy of Medical Sciences, Beijing, China.
⁵ School of Medicine, Tsinghua University, Beijing, China.

Abstract

Objective: 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. Methods: 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 (n = 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. Results: 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 CD8⁺CD28⁺ T cells, and natural killer (NK) cell count. Conclusion: 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.

Keywords: APRIL; BAFF; HIV-1 disease progression; antibody response; functional cells; immune activation.