title: Host biomarkers of invasive pulmonary aspergillosis to monitor therapeutic response.
abstract: Invasive pulmonary aspergillosis (IPA) is a life-threatening disease of immunocompromised patients that requires aggressive therapy. Detection of the disease and monitoring of the therapeutic response during IPA are complex, and current molecular diagnostics are not suitably robust. Here, we explored proteomic profiles of bronchoalveolar lavage fluid (BALF) specimens from a persistently neutropenic rabbit model of IPA. Three experimental arms, uninfected control animals, infected untreated animals, and animals infected and treated with ravuconazole/amphotericin B, were studied. Total proteins were evaluated by two-dimensional (2D) gel electrophoresis, followed by matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) mass spectrometry (MS) and quantified by enzyme-linked immunosorbent assay (ELISA). Host-derived proteins haptoglobin (Hp), C-reactive protein (CRP), and annexin A1 (Anx A1) were prominently found in BALF during the IPA infection and showed significant changes in response to antifungal therapy (P < 0.0001). In serum, differences in Hp (P = 0.0001) between infected and treated rabbits were observed. Preliminary in vitro studies revealed that Aspergillus fumigatus-secreted proteases may contribute to the cleavage of Anx A1 during IPA. In summary, host protein biomarkers Hp, CRP, and Anx A1 may have value in monitoring therapeutic response to antifungal agents in IPA patients with confirmed disease.
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Mila
authors.initials: M
authors.lastname: Krel
authors.affiliation: Transplantation-Oncology Infectious Diseases Program, Weill Cornell Medical Center of Cornell University, Ithaca, New York, USA.
authors.forename: Vidmantas
authors.initials: V
authors.lastname: Petraitis
authors.affiliation: Transplantation-Oncology Infectious Diseases Program, Weill Cornell Medical Center of Cornell University, Ithaca, New York, USA.
authors.forename: Ruta
authors.initials: R
authors.lastname: Petraitiene
authors.affiliation: Center for Advanced Proteomics Research, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Mohit Raja
authors.initials: MR
authors.lastname: Jain
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Center for Advanced Proteomics Research, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Transplantation-Oncology Infectious Diseases Program, Weill Cornell Medical Center of Cornell University, Ithaca, New York, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA perlinds@njms.rutgers.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism; D000935:Antifungal Agents / Q000627:therapeutic use*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D002097:C-Reactive Protein / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000188:drug therapy*; D009503:Neutropenia; D040901:Proteomics; D011817:Rabbits; D013844:Thiazoles / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D017305:Annexin A1; D000935:Antifungal Agents; D015415:Biomarkers; D013844:Thiazoles; D014230:Triazoles; D000666:Amphotericin B; D002097:C-Reactive Protein; C104066:ER 30346