title: 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.
authors.affiliation: Departments of Medicin, University of Pittsburgh, Pittsburgh, PA 15213, USA. morrisa@upmc.edu
authors.forename: Alison
authors.initials: A
authors.lastname: Morris
authors.forename: Maria
authors.initials: M
authors.lastname: Hillenbrand
authors.forename: Malcolm
authors.initials: M
authors.lastname: Finkelman
authors.forename: M Patricia
authors.initials: MP
authors.lastname: George
authors.forename: Vikas
authors.initials: V
authors.lastname: Singh
authors.forename: Cathy
authors.initials: C
authors.lastname: Kessinger
authors.forename: Lorrie
authors.initials: L
authors.lastname: Lucht
authors.forename: Michelle
authors.initials: M
authors.lastname: Busch
authors.forename: Deborah
authors.initials: D
authors.lastname: McMahon
authors.forename: Renee
authors.initials: R
authors.lastname: Weinman
authors.forename: Chad
authors.initials: C
authors.lastname: Steele
authors.forename: Karen A
authors.initials: KA
authors.lastname: Norris
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Gingo
mesh_terms: D000328:Adult; D016207:Cytokines / Q000378:metabolism; D004452:Echocardiography; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis; D007108:Immune Tolerance; D007249:Inflammation / Q000473:pathology; D008033:Limulus Test; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000453:epidemiology*; D010045:Outpatients; D011509:Proteoglycans; D012129:Respiratory Function Tests; D044967:Serum / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology; D047071:beta-Glucans / Q000097:blood*
chemical_list: D016207:Cytokines; D011509:Proteoglycans; D047071:beta-Glucans; C010770:polysaccharide-K