Abstract
BackgroundThere has been a rising incidence of invasive aspergillosis (IA) in critically ill patients, even in the absence of an apparent predisposing immunodeficiency. The diagnosis of IA is difficult because clinical signs are not sensitive and specific, and serum galactomannan has relatively low sensitivity in this group of patients. Therefore, more prompt and accurate disease markers for early diagnosis are needed. To establish disease markers demands a thorough knowledge of fungal antigens which may be detected in the serum or other body fluids of patients. Herein we report novel immunodominant antigens identified from extracellular proteins of Aspergillus fumigatus.ResultsExtracellular proteins of A. fumigatus were separated by two-dimensional electrophoresis (2-DE) and probed with the sera from critically ill patients with proven IA. The immunoreactive protein spots were identified by MALDI-TOF mass spectrometry (MALDI-TOF -MS). Forty spots from 2DE gels were detected and 17 different proteins were identified as immunogenic in humans. Function annotation revealed that most of these proteins were metabolic enzymes involved in carbohydrate, fatty acid, amino acid, and energy metabolism. One of the proteins, thioredoxin reductase GliT (TR), which showed the best immunoactivity, was analyzed further for secretory signals, protein localization, and homology. The results indicated that TR is a secretory protein with a signal sequence exhibiting a high probability for secretion. Furthermore, TR did not match any human proteins, and had low homology with most other fungi. The recombinant TR was recognized by the sera of all proven IA patients with different underlying diseases in this study.ConclusionsThe immunoreactive proteins identified in this study may be helpful for the diagnosis of IA in critically ill patients. Our results indicate that TR and other immunodominant antigens have potential as biomarkers for the serologic diagnosis of invasive aspergillosis.
Highlights
There has been a rising incidence of invasive aspergillosis (IA) in critically ill patients, even in the absence of an apparent predisposing immunodeficiency
Studies on the extracellular proteins of A. fumigatus and their immunogenic potential are important for further understanding the pathogenesis of A. fumigatus and targets for the immunodiagnosis of the diseases
Of 17 identified proteins, 14 were matched with A. fumigatus (Af 293), and 3 showed homology to proteins from another Aspergillus species. Most of these proteins are metabolic enzymes that are involved in carbohydrate, fatty acid, amino acid, and energy metabolism. Seven of these proteins have been reported as antigens of Aspergillus and other fungi, and others have not been described as antigens before, such as fumarylacetoacetate hydrolase FahA, aldehyde dehydrogenase AldA, aromatic aminotransferase Aro8, Table 1 Clinical characteristics of proven IA patients
Summary
There has been a rising incidence of invasive aspergillosis (IA) in critically ill patients, even in the absence of an apparent predisposing immunodeficiency. The risk factors for IA include chronic obstructive pulmonary disease (COPD) and other chronic lung diseases [1,2,3,4,7,8], prolonged use of steroids [2,9], advanced liver disease [2,3,4,10], chronic renal replacement therapy [11,12], near-drowning [4,13,14,15], and diabetes mellitus [2,3,9] The diagnosis of such IA is difficult because signs and symptoms are non-specific. More prompt and accurate disease markers for early diagnosis are needed, which requires a thorough knowledge of fungal antigens detected in the serum or other body fluids of infected patients
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