Host Biomarkers of Invasive Pulmonary Aspergillosis to Monitor Therapeutic 1 Response 2 3 4
نویسندگان
چکیده
19 Invasive pulmonary aspergillosis (IPA) is a life threatening disease of 20 immunocompromised patients that requires aggressive therapy. Detection and monitoring 21 therapeutic response during IPA is complex and current molecular diagnostics are not 22 suitably robust. Here, we explored proteomic profiles of bronchoalveolar lavage fluid 23 (BALF) specimens from a persistently neutropenic rabbit model of IPA. Three 24 experimental arms: uninfected control animals, infected untreated animals, and animals 25 infected and treated with ravuconazole/amphotericin B were studied. Total proteins were 26 evaluated by 2D gel electrophoresis, followed by matrix-assisted laser 27 desorption/ionization time-of-flight/time-of-flight (MALDI TOF/TOF) mass 28 spectroscopy (MS) and quantified by enzyme-linked immunosorbent assay (ELISA). 29 Host derived proteins: Haptoglobin (Hp), C-reactive protein (CRP) and Annexin A1 (Anx 30 A1) were prominently found in BALF during the IPA infection and showed significant 31 changes in response to antifungal therapy (p < 0.0001). In serum differences in Hp (p = 32 0.0001) were observed between infected and treated rabbits. Preliminary in vitro studies 33 revealed that Aspergillus fumigatus secreted proteases may contribute to the cleavage of 34 Anx A1 during IPA. In summary, host protein biomarkers Hp, CRP and Anx A1 may 35 have value to monitor therapeutic response to antifungal agents in IPA patients with 36 confirmed disease.
منابع مشابه
Host biomarkers of invasive pulmonary aspergillosis to monitor therapeutic response.
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 neutrop...
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