Circulating (1 → 3)-β-D-Glucan as an immune activation marker decreased after ART in people living with HIV

Abstract

BackgroundPlasma level of polysaccharide (1 → 3)-β-D-Glucan (βDG), as a diagnostic marker of invasive fungal infection has been reported to be elevated in people living with HIV (PLWH). We assessed the association of circulating βDG to inflammation and systemic immune activation and the effect of antiretroviral therapy (ART) on βDG in PLWH.MethodPlasma and peripheral blood monocular cell samples from 120 PLWH naive to ART and after 1 year's ART were collected. Plasma levels of βDG, markers of bacterial translocation, gut damage, and cellular immune activation were quantified.ResultThe plasma βDG levels were negatively correlated with CD4+ T cells count (r = −0.25, p = 0.005) and positively with HIV viral load (r = 0.28, p = 0.002) before ART. It was also positively correlated with immune activation markers, including PD-1 expression on CD4+ T cell (r = 0.40, p = 0.01) and CD8+ T cell (r = 0.47, p = 0.002), as well as HLADR+CD38+ co-expression on CD8+ T cell (r = 0.56, p = 0.0002), but not with the plasma levels of LPS (r = 0.02, p = 0.84), LPS binding protein (LBP, r = 0.11, p = 0.36), soluble LPS receptor sCD14 (r = 0.04, p = 0.68), intestinal fatty acid binding protein (IFABP, r = −0.12, p = 0.18), and regenerating islet-derived protein 3α (REG3α, r = 0.18, p = 0.06). After 1 year's ART, the levels of βDG were significantly decreased compared to that in pre-ART (1.31 ± 0.24 Log10 pg/ml vs. 1.39 ± 0.18 Log10 pg/ml, p < 0.001).ConclusionThe level of plasma βDG was associated with cellular immune activation and decreased after ART in PLWH, suggesting it could serve as a biomarker of immune activation and efficacy monitoring.

Fungal translocation measured by serum 1,3‐ß‐D‐glucan correlates with severity and outcome of liver cirrhosis—A pilot study

“…Similar findings were obtained in a very recent study where BDG levels in HIV patients decreased after 1 year of anti-retroviral therapy. 36 The absence of correlation with other permeability markers might also be partially explained by another mechanism acting a part, which is a decrease in BDG clearance by the hepatic reticuloendothelial system with increasing hepatic inflammation and hence higher levels in peripheral blood. 32 In a mouse model, Yang et al observed that a decrease in intestinal fungal overgrowth by non-absorbable Amphotericin B did not alter the gut barrier function and permeability remained increased.…”

“…Similar findings were obtained in a very recent study where BDG levels in HIV patients decreased after 1 year of anti‐retroviral therapy. 36 The absence of correlation with other permeability markers might also be partially explained by another mechanism acting a part, which is a decrease in BDG clearance by the hepatic reticuloendothelial system with increasing hepatic inflammation and hence higher levels in peripheral blood. 32…”