Effects of potent antiretroviral therapy on the immune activation marker soluble CD27 in patients infected with HIV‐1 subtypes A–D

Abstract

HIV-1 genetic subtypes might have a different impact on disease progression and response to antiretroviral therapy (ART). Few data are available on the immune activation profile in patients with different HIV-1 subtypes. We have tested by ELISA the plasma levels of an immune activation marker, soluble CD27 (sCD27), in a cohort of 64 patients infected with HIV-1 subtypes A-D, at baseline and after 1 year of virologically successful ART. Plasma sCD27 was significantly higher in the whole HIV-1-infected population as compared to healthy subjects [522 U/ml (188-1,307) vs. 285 U/ml (174-397), P < 0.001]. Among the four different HIV-1 subtypes, patients with subtype C virus had significantly higher plasma sCD27 [684 U/ml, (188-1228)] as compared to patients with subtype A [428 U/ml (247-1307), P < 0.05] and B [454 (211-925), P < 0.05]. After 1 year of ART, plasma sCD27 significantly decreased in all groups but patients with subtype C viruses had the largest reduction of sCD27 from baseline. The data indicate that a similar immune activation profile is present in patients infected with HIV-1 subtypes A, B, and D and that in presence of successful ART these subtypes respond similarly in terms of immune activation. Intriguingly, subtype C infection seems to be associated with higher levels of plasma sCD27, suggesting that HIV-1 genetic subtype C may have a different impact on disease outcome and response to therapy.

Dynamics of Memory B-Cell Populations in Blood, Lymph Nodes, and Bone Marrow during Antiretroviral Therapy and Envelope Boosting in Simian Immunodeficiency Virus SIVmac251-Infected Rhesus Macaques

“…Activated T, NK, and B cells all express cell surface CD27 (63), which can be proteolytically cleaved to produce a soluble form (sCD27). sCD27 levels are elevated in HIV-infected individuals (1,12,48) and correlate with plasma viremia (12) but can be decreased by successful HAART treatment over time. Further studies will be needed to determine the prevalence of CD27 Ϫ and CD27 ϩ PC/PB in healthy and immunodeficient hosts and whether they exhibit functional differences.…”

Plasmacytoid Dendritic Cells Mediate Synergistic Effects of HIV and Lipopolysaccharide on CD27+IgD–Memory B Cell Apoptosis

“…Microbial products, such as TLR ligands, can maintain mB cell numbers and recall Ab titers in the absence of protein antigens (Ags) in healthy individuals (19). Although TLR ligands released from the gut have long-term effects on the humoral system, they do not appear to maintain mB cell numbers and func-tions in HIV-infected subjects as they do in healthy subjects (1,2,20). However, B cells from HIV-infected subjects are still polyclonally activated and are able to produce auto-Abs during chronic infection (20).…”

“…Although TLR ligands released from the gut have long-term effects on the humoral system, they do not appear to maintain mB cell numbers and func-tions in HIV-infected subjects as they do in healthy subjects (1,2,20). However, B cells from HIV-infected subjects are still polyclonally activated and are able to produce auto-Abs during chronic infection (20). Therefore, B cell dysfunction does not result solely from repeated stimulation by microbial products and subsequent desensitization.…”

Immune activation in HIV/HCV-infected patients is associated with low-level expression of liver expressed antimicrobial peptide-2 (LEAP-2)

“…To investigate the relationship between LEAP-2 expression and immune activation, the plasma levels of sCD27, which is a marker of T cell activation,13 29 was measured. CD27 is type II transmembrane glycoprotein, which belongs to the TNF receptor family, and is expressed on the surface of antigen-experienced B cells,30 most T cells,31 and natural killer cells 32.…”