Most cited article - PubMed ID 36422015
Distinguishing Invasive from Chronic Pulmonary Infections: Host Pentraxin 3 and Fungal Siderophores in Bronchoalveolar Lavage Fluids
Pentraxin 3 (Ptx3) is an acute-phase protein that specifically targets fungal galactosaminogalactan and has been proposed as a promising biomarker for invasive fungal infections. However, its stability in clinical samples over time has not yet been established. This study aimed to evaluate the stability of Ptx3 in serum and bronchoalveolar lavage fluid (BALF) samples during mid- and long-term storage. A total of 44 serum and 52 BALF samples were examined or re-examined for Ptx3 concentrations using enzyme immunoassay in pooled and individual sample formats. Samples were stored at -80°C, -20°C, and +37°C for periods ranging from 0 to 56 months. Statistical analyses included a paired two-sample Wilcoxon signed-rank test, analysis of variance, Bonferroni test, and linear regression analysis. Ptx3 remained highly stable in serum and BALF samples for up to 8 months at -20°C, with variations ranging from -1.8% to +2.8%. Long-term stability was observed at -80°C for 48 months, followed by a slow decline in Ptx3 levels. In contrast, storage at +37°C resulted in rapid degradation, with a 36.5%-60.7% increase or a 92.9%-97% decrease in Ptx3 levels in serum and BALF, respectively. These findings confirm that Ptx3 is a stable and reliable biomarker for invasive fungal infections when appropriate storage conditions are maintained.
Pentraxin 3 is a promising marker of fungal infections. This study shows it remains stable in body fluids samples for months when properly frozen, but breaks down quickly when stored at warmer temperatures, supporting its use in diagnostics under standard storage conditions.
- Keywords
- Aspergillosis, Pentraxin 3, biomarker, bronchoalveolar lavage fluid, enzyme immunoassay, preservation, serum, stability, storage,
- MeSH
- Biomarkers analysis blood MeSH
- Bronchoalveolar Lavage Fluid * chemistry MeSH
- C-Reactive Protein * analysis chemistry MeSH
- Time Factors MeSH
- Adult MeSH
- Invasive Fungal Infections diagnosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Specimen Handling methods MeSH
- Serum Amyloid P-Component * analysis chemistry MeSH
- Protein Stability MeSH
- Temperature MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Biomarkers MeSH
- C-Reactive Protein * MeSH
- PTX3 protein MeSH Browser
- Serum Amyloid P-Component * MeSH
Advances in the early diagnosis of systemic mycoses are urgently needed, given the morbidity and mortality of such infections and the correlation between delays in treatment and poor outcomes. We demonstrated the prospective application of liquid chromatography-mass spectrometry in the diagnosis of a mixed fungal infection. In this study, we compared the performance of chest radiography, galactomannan (sGM), and beta-d-glucan (sBDG) serology with a novel diagnostic method based on creatinine-indexed microbial siderophores in urine. A woman with angioblastic T-cell lymphoma presented with neutropenia following allogeneic transplantation. sGM and sBDG remained positive throughout the 28-day intensive care unit stay. A. fumigatus DNA was detected in the induced sputum samples on sampling days 0 and 18. On day 18, a CT scan showed a typical nest sign, and R. microsporus DNA was detected in sputum. The patient was discharged from the hospital on day 28 and expired 7 days later. With our novel strategy based on mass spectrometry, A. fumigatus was consistently detected in the urine from day 0 to the end of the stay by the detection of triacetylfusarinine C (uTafC), an A. fumigatus-specific hydroxamate siderophore. An additional invasive R. microsporus infection was revealed by the detection of a mucoromycete-specific carboxylate siderophore in urine, rhizoferrin (uRhf), from day seven onward. Both creatinine-normalized siderophore indices (uTafC/Cr, uRhf/Cr) were sensitive to antifungal therapy and correlated with fast relapses of the invasive disease in time. This study illustrates how such an early and specific new approach can unravel the complexities of dual fungal infections.
- Publication type
- Journal Article MeSH
Aspergillus fumigatus has been designated by the World Health Organization as a critical priority fungal pathogen. Some commercially available diagnostics for many forms of aspergillosis rely on fungal metabolites. These encompass intracellular molecules, cell wall components, and extracellular secretomes. This review summarizes the shortcomings of antibody tests compared to tests of fungal products in body fluids and highlights the application of β-d-glucan, galactomannan, and pentraxin 3 in bronchoalveolar lavage fluids. We also discuss the detection of nucleic acids and next-generation sequencing, along with newer studies on Aspergillus metallophores.
- Keywords
- PCR, aspergillosis, bronchoalveolar lavage fluid, galactomannan, lateral flow, metagenomic next-generation sequencing, metallophore, serum assays, siderophore, β-d-glucan,
- Publication type
- Journal Article MeSH
- Review MeSH
Invasive pulmonary aspergillosis (IPA) may be a rare cause of granulomatous pneumonia in horses. The mortality of IPA is almost 100%; direct diagnostic tools in horses are needed. Bronchoalveolar lavage fluid (BALF) and serum samples were collected from 18 horses, including individuals suffering from IPA (n = 1), equine asthma (EA, n = 12), and 5 healthy controls. Serum samples were collected from another 6 healthy controls. Samples of BALF (n = 18) were analyzed for Aspergillus spp. DNA, fungal galactomannan (GM), ferricrocin (Fc), triacetylfusarinin C (TafC), and gliotoxin (Gtx). Analysis of 24 serum samples for (1,3)-β-D-glucan (BDG) and GM was performed. Median serum BDG levels were 131 pg/mL in controls and 1142 pg/mL in IPA. Similar trends were observed in BALF samples for GM (Area under the Curve (AUC) = 0.941) and DNA (AUC = 0.941). The fungal secondary metabolite Gtx was detected in IPA BALF and lung tissue samples (86 ng/mL and 2.17 ng/mg, AUC = 1).
