Serum (1→3)-β-D-glucan levels in HIV-infected individuals are associated with immunosuppression, inflammation, and cardiopulmonary function

Abstract

Background: Translocation of gastrointestinal bacteria in HIV-infected individuals is associated with systemic inflammation, HIV progression, mortality, and comorbidities. HIV-infected individuals are also susceptible to fungal infection and colonization, but whether fungal translocation occurs and influences HIV progression or comorbidities is unknown.

Methods: Serum (1→3)-β-D-glucan (BG) was measured by a Limulus Amebocyte Lysate assay (Fungitell) in 132 HIV-infected outpatients. Selected plasma cytokines and markers of peripheral T-cell activation were measured. Pulmonary function testing and Doppler echocardiography were performed. Relationship of high (≥40 pg/mL) and low (<40 pg/mL) levels of BG with HIV-associated variables, inflammation markers, and pulmonary function and pulmonary hypertension measures were determined.

Results: Forty-eight percent of patients had detectable BG, and 16.7% had high levels. Individuals with high BG were more likely to have CD4 counts less than 200 cells/μL (31.8% vs. 8.4%, P = 0.002), had higher log10 HIV viral levels (2.85 vs. 2.13 log copies/mL, P = 0.004), and were less likely to use antiretroviral therapy (68.2% vs. 90.0%, P = 0.006). Plasma IL-8 (P = 0.033), TNF-α (P = 0.029), and CD8CD38 (P = 0.046) and CD8HLA-DR (P = 0.029) were also increased with high levels. Abnormalities in diffusing capacity (P = 0.041) and in pulmonary artery pressures (P = 0.006 for pulmonary artery systolic pressure and 0.013 for tricuspid regurgitant velocity) were more common in those with high BG.

Conclusions: We found evidence of peripheral fungal cell wall polysaccharides in an HIV-infected cohort. We also demonstrated an association between high serum BG, HIV-associated immunosuppression, inflammation, and cardiopulmonary comorbidity. These results implicate a new class of pathogen in HIV-associated microbial translocation and suggest a role in HIV progression and comorbidities.

Figure 1

Distribution of serum (1→3)-β-D-glucan in 132 HIV-infected individuals. Abbreviations: BG, serum (1→3)-β-D-glucan

Figure 2

Plasma cytokines are increased in HIV-infected individuals with high (>40pg/ml) or low (≤40 pg/ml) serum (1→3)-β-D-glucan. Abbreviations: BG, serum (1→3)-β-D-glucan; IL, interleukin; TNF, tumor necrosis factor.

Figure 3

T-cell markers of immune activation are increased in HIV-infected individuals with high (>40pg/ml) or low (≤40 pg/ml) serum (1→3)-β-D-glucan. n=71 for CD38+, n=21 for HLA-DR+ Abbreviations: BG, serum (1→3)-β-D-glucan. Bars=median, whiskers=10-90^th percentile. P=0.046 for CD8+CD38+, p=0.049 for CD8+HLA-DR+

Figure 4

Prevalence of cardiopulmonary abnormalities by high (>40pg/ml) or low (≤40 pg/ml) serum (1→3)-β-D-glucan. Abbreviations: Airway obstruction=forced expiratory volume in one second/forced vital capacity <0.70; abnormal DLco, diffusing capacity for carbon monoxide ≤60% predicted adjusted for hemoglobin and carboxyhemoglobin; abnormal PASP, pulmonary artery systolic pressure ≥35 mm Hg; abnormal TRV, tricuspid regurgitant jet velocity ≥3m/sec; BG, serum (1→3)-β-D-glucan.