title: Effects of host response and antifungal therapy on serum and BAL levels of galactomannan and (1→3)-β-D-glucan in experimental invasive pulmonary aspergillosis.
abstract: Galactomannan and (1→3)-β-D-glucan are useful biomarkers of invasive pulmonary aspergillosis (IPA). However, the effects of immunosuppression on levels of galactomannan or (1→3)-β-D-glucan in IPA are not well understood or quantified. We therefore studied the simultaneous levels of galactomannan and (1→3)-β-D-glucan in two rabbit models of experimental IPA: (1) AraC-induced neutropenia in untreated (UC-AraC) and liposomal amphotericin B-treated (LAMB-AraC) rabbits; and (2) nonneutropenic cyclosporine-methylprednisolone immunosuppression in untreated (UC-CsA+M) and LAMB-treated (LAMB-CsA+M) rabbits. Simultaneous levels of galactomannan and (1→3)-β-D-glucan were determined in bronchoalveolar lavage (BAL) fluid and serial serum specimens and correlated with pulmonary host response. Serum galactomannan index (GMI) and (1→3)-β-D-glucan concentration-time-curves were higher in UC-AraC vs. UC-CsA+M (Mann-Whitney U-test, P < .05). Serum galactomannan and (1→3)-β-D-glucan in treatment groups demonstrated therapeutic responses with similarly lower levels in comparison to UC (P < .01) in both models. Host differences did not affect BAL fluid GMI or (1→3)-β-D-glucan but did affect galactomannan and (1→3)-β-D-glucan levels in serum. The higher serum GMI and (1→3)-β-D-glucan concentration-time-curves in UC-AraC correlated with extensive pulmonary infiltration by angioinvasive hyphae and minimal inflammation, while the lower concentration-time-curves in UC-CsA+M were associated with shorter and fewer hyphae in lung tissue and an intensive neutrophil response to Aspergillus hyphae. Thus, serum levels of galactomannan and (1→3)-β-D-glucan in IPA depended upon immunosuppression, which also affected severity of infection and hyphal morphology, while BAL fluid galactomannan and (1→3)-β-D-glucan were sensitive biomarkers not affected by host response.
authors.affiliation: Transplantation-Oncology Infectious Diseases Program, Department of Medicine, Weill Cornell Medical Center of Cornell University, New York, New York, USA thw2003@med.cornell.edu rop2016@med.cornell.edu.
authors.forename: Ruta
authors.initials: R
authors.lastname: Petraitiene
authors.affiliation: Transplantation-Oncology Infectious Diseases Program, Department of Medicine, Weill Cornell Medical Center of Cornell University, New York, New York, USA.
authors.forename: Vidmantas
authors.initials: V
authors.lastname: Petraitis
authors.affiliation: Division of Veterinary Resources, Office of Research Services, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Bacher
authors.affiliation: Associates of Cape Cod, Inc., East Falmouth, Massachusetts, USA.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Finkelman
authors.affiliation: Transplantation-Oncology Infectious Diseases Program, Department of Medicine, Weill Cornell Medical Center of Cornell University, New York, New York, USA Departments of Pediatrics and Microbiology and Immunology, Weill Cornell Medical College of Cornell University, New York, New York, USA thw2003@med.cornell.edu rop2016@med.cornell.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D054884:Host-Pathogen Interactions; D055744:Invasive Pulmonary Aspergillosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008351:Mannans / Q000032:analysis* / Q000097:blood; D011509:Proteoglycans; D011817:Rabbits; D047071:beta-Glucans / Q000032:analysis* / Q000097:blood
chemical_list: D000935:Antifungal Agents; D008351:Mannans; D011509:Proteoglycans; D047071:beta-Glucans; C012990:galactomannan; C010770:polysaccharide-K; D005690:Galactose
keywords: (1→3)-β-D-glucan; aspergillosis; galactomannan; immunosuppression; neutropenia