Abstract
Invasive aspergillosis (IA) is a life-threatening systemic mycosis caused primarily by Aspergillus fumigatus. Early diagnosis of IA is based, in part, on an immunoassay for circulating fungal cell wall carbohydrate, galactomannan (GM). However, a wide range of sensitivity and specificity rates have been reported for the GM test across various patient populations. To obtain iron in vivo, A. fumigatus secretes the siderophore, N,N',N"-triacetylfusarinine C (TAFC) and we hypothesize that TAFC may represent a possible biomarker for early detection of IA. We developed an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for TAFC analysis from serum, and measured TAFC in serum samples collected from patients at risk for IA. The method showed lower and upper limits of quantitation (LOQ) of 5 ng/ml and 750 ng/ml, respectively, and complete TAFC recovery from spiked serum. As proof of concept, we evaluated 76 serum samples from 58 patients with suspected IA that were investigated for the presence of GM. Fourteen serum samples obtained from 11 patients diagnosed with probable or proven IA were also analyzed for the presence of TAFC. Control sera (n = 16) were analyzed to establish a TAFC cut-off value (≥6 ng/ml). Of the 36 GM-positive samples (≥0.5 GM index) from suspected IA patients, TAFC was considered positive in 25 (69%). TAFC was also found in 28 additional GM-negative samples. TAFC was detected in 4 of the 14 samples (28%) from patients with proven/probable aspergillosis. Log-transformed TAFC and GM values from patients with proven/probable IA, healthy individuals and SLE patients showed a significant correlation with a Pearson r value of 0.77. In summary, we have developed a method for the detection of TAFC in serum that revealed this fungal product in the sera of patients at risk for invasive aspergillosis. A prospective study is warranted to determine whether this method provides improved early detection of IA.
Highlights
Invasive aspergillosis (IA) is a life-threatening infection that affects immunosuppressed individuals including those with neutropenia, chronic granulomatous disease, acquired immune deficiency syndrome, those undergoing hematopoietic stem cell transplantation (HSCT) or solid organ transplantation, especially those with graft-versus-host disease[1,2,3]
LC-MS/MS detection of triacetylfusarinine C (TAFC) was performed by positive electrospray ionization and with multiple reaction monitoring (MRM) data acquisition
An LC-MS/MS method was developed for detecting the fungal siderophore, N,N',N"-triacetylfusarinine C (TAFC) in serum from patients at risk of developing invasive aspergillosis
Summary
Invasive aspergillosis (IA) is a life-threatening infection that affects immunosuppressed individuals including those with neutropenia, chronic granulomatous disease, acquired immune deficiency syndrome, those undergoing hematopoietic stem cell transplantation (HSCT) or solid organ transplantation, especially those with graft-versus-host disease[1,2,3]. Invasive infections occur when fungal conidia are inhaled, germinate and penetrate the epithelia lining of the sinuses or lungs. The fungus may disseminate hematogenously to other organs. A major challenge for the management of IA is the lack of early diagnosis[10,11]. Antifungal therapy is often administered only after a prolonged febrile illness unresponsive to antibiotic therapy and confirmation of IA in many cases is made at autopsy[6]. Delays in diagnosis contribute to the morbidity and mortality rates from these infections; it is critical to identify mechanisms for the early detection of fungal growth in vivo
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
