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.
Highlights
Persistent immune activation is a key feature of HIV-1 infection in both viremic and antiretroviral therapy (ART)treated aviremic patients [1]
The circulating A proliferation-inducing ligand (APRIL) levels were significantly elevated in the long-term non-progressors (LTNPs) relative to the typical progressors (TPs), ART-treated patients, and healthy donors (HDs)
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)
Summary
Persistent immune activation is a key feature of HIV-1 infection in both viremic and antiretroviral therapy (ART)treated aviremic patients [1]. This feature has been linked to suboptimal immune reconstitution and the development of acquired immune deficiency syndrome (AIDS) and non-AIDS events [2,3,4]. B-cell-activating factor (BAFF), which belongs to the TNF family (TNFSF 13b), contributes to Bcell activation and may lead to hypergammaglobulinemia, an impaired humoral response, and the loss of memory B cells [8]. Knowledge regarding the characteristics of APRIL during HIV-1 infection is limited, and the role of APRIL in the pathogenesis of AIDS is less well-defined
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