Host Biomarkers of Invasive Pulmonary Aspergillosis to Monitor Therapeutic Response.
Antimicrob Agents Chemother. 2014 Mar 31;
Authors: Krel M, Petraitis V, Petraitiene R, Jain MR, Zhao Y, Li H, Walsh TJ, Perlin DS
Abstract
Invasive pulmonary aspergillosis (IPA) is a life threatening disease of immunocompromised patients that requires aggressive therapy. Detection and monitoring therapeutic response during IPA is 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 2D gel electrophoresis, followed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI TOF/TOF) mass spectroscopy (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) were observed between infected and treated rabbits. 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 to monitor therapeutic response to antifungal agents in IPA patients with confirmed disease.
PMID: 24687510 [PubMed - as supplied by publisher]