TY - JOUR
T1 - Host biomarkers of invasive pulmonary aspergillosis to monitor therapeutic response
AU - Krel, Mila
AU - Petraitis, Vidmantas
AU - Petraitiene, Ruta
AU - Jain, Mohit Raja
AU - Zhao, Yanan
AU - Li, Hong
AU - Walsh, Thomas J.
AU - Perlin, David S.
PY - 2014/6
Y1 - 2014/6
N2 - 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 twodimensional (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 fumigatussecreted 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.
AB - 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 twodimensional (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 fumigatussecreted 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.
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U2 - 10.1128/AAC.02482-14
DO - 10.1128/AAC.02482-14
M3 - Article
C2 - 24687510
AN - SCOPUS:84901276348
SN - 0066-4804
VL - 58
SP - 3373
EP - 3378
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 6
ER -