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.

BackgroundThe yeast Candida is one of the most frequent pathogens isolated from bloodstream infections and is associated with significant morbidity and mortality. Problems with clinical and microbiological diagnosis of invasive candidiasis (IC) have prompted the development of non-culture-based laboratory methods. Previous reports suggest that serological detection of antibodies might be useful for diagnosing systemic candidiasis.MethodsDiagnosis of IC using antibodies against recombinant Candida albicans enolase (Eno) and fructose-bisphosphate aldolase (Fba1) was evaluated. Using recombinant Eno and Fba1 as coating antigens, enzyme-linked immunosorbent assays (ELISAs) were used to analyze sera from patients with candidemia (n = 101), Candida colonization (n = 50), bacteremia (n = 84), invasive aspergillosis (n = 40); and from healthy controls (n = 200).ResultsThe results demonstrated that ELISA detection of anti-Eno and anti-Fba1 IgG distinguished IC from other pathogenic infections in patients and healthy individuals. The sensitivity, specificity, and positive and negative predictive values were 72.3%, 94.7%, 78.5% and 93% for anti-Eno, and 87.1%, 92.8%, 76.5% and 96.4% for anti-Fba1 antibodies, respectively. Combining these two tests improved sensitivity up to 90.1% and negative predictive value up to 97.1%, with specificity and positive predictive values of 90.6% and 72.2%. The tests were specific to the Candida genus and antibody titers were higher for candidemia patients than for controls. Positive antibody tests were obtained before blood culture results for 42.2% of patients for anti-Eno and 51.1% for anti-Fba1.ConclusionThese data suggest that tests that detect IgG antibodies against Candida enolase and fructose-bisphosphate aldolase, especially when used in combination, could be a powerful tool for diagnosing IC.

BackgroundSmall dense low-density lipoprotein cholesterol (sdLDL-C) concentration was useful in the assessment of the presence of cardiovascular diseases (CVD) and its severity. We examined whether SdLDL-C is more closely associated with carotid artery intima-media thickness (CA-IMT), a surrogate measure of atherosclerosis, than LDL-C and traditional CVD risk factors in Chinese healthy subjects.MethodsWe measured CA-IMT, blood pressure (BP), sdLDL-C, glucose metabolism and lipid in 183 native Chinese healthy subjects. CA-IMT was assessed by ultrasonography, and sdLDL-C concentrations were measured by a homogenous assay. Pearson's correlation coefficient analyses and Multiple regression analyses were used to examine the relationships between CA-IMT values and other clinical variables.ResultsThe sdLDL-C level was significantly higher in males than in females (p <0.05) and there was an age effect on sdLDL-C (p <0.05). When the effects of age, gender and other traditional CVD risk factors were adjusted using multiple regression analysis. CA-IMT remained significantly associated with sdLDL-C(β = 0.437, p <0.001).ConclusionsThere are gender and age differences in sdLDL-C levels among a healthy Chinese population. Moreover, we found adjusted traditional CVD risk factors such as higher age, male sex, and other traditional CVD risk factors, the association between CA-IMT and SdLDL-C remained significant. sdLDL-C is may be a useful predictor in the assessment of CA-IMT in Chinese population.