scholarly journals Specific Recognition of β-Galactofuranose-Containing Glycans of Synthetic Neoglycoproteins by Sera of Chronic Chagas Disease Patients

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 411
Author(s):  
Alba L. Montoya ◽  
Eileni R. Gil ◽  
Emily L. Heydemann ◽  
Igor L. Estevao ◽  
Bianca E. Luna ◽  
...  

Chagas disease (CD) can be accurately diagnosed by detecting Trypanosoma cruzi in patients’ blood using polymerase chain reaction (PCR). However, parasite-derived biomarkers are of great interest for the serological diagnosis and early evaluation of chemotherapeutic efficacy when PCR may fail, owing to a blood parasite load below the method’s limit of detection. Previously, we focused on the detection of specific anti-α-galactopyranosyl (α-Gal) antibodies in chronic CD (CCD) patients elicited by α-Gal glycotopes copiously expressed on insect-derived and mammal-dwelling infective parasite stages. Nevertheless, these stages also abundantly express cell surface glycosylphosphatidylinositol (GPI)-anchored glycoproteins and glycoinositolphospholipids (GIPLs) bearing nonreducing terminal β-galactofuranosyl (β-Galf) residues, which are equally foreign to humans and, therefore, highly immunogenic. Here we report that CCD patients’ sera react specifically with synthetic β-Galf-containing glycans. We took a reversed immunoglycomics approach that entailed: (a) Synthesis of T. cruzi GIPL-derived Galfβ1,3Manpα-(CH2)3SH (glycan G29SH) and Galfβ1,3Manpα1,2-[Galfβ1,3]Manpα-(CH2)3SH (glycan G32SH); and (b) preparation of neoglycoproteins NGP29b and NGP32b, and their evaluation in a chemiluminescent immunoassay. Receiver-operating characteristic analysis revealed that NGP32b can distinguish CCD sera from sera of healthy individuals with 85.3% sensitivity and 100% specificity. This suggests that Galfβ1,3Manpα1,2-[Galfβ1,3]Manpα is an immunodominant glycotope and that NGP32b could potentially be used as a novel CCD biomarker.

2021 ◽  
Author(s):  
Ullas Batra ◽  
Shrinidhi Nathany ◽  
Mansi Sharma ◽  
Parveen Jain ◽  
Surender Dhanda ◽  
...  

Introduction: With the International Association for the Study of Lung Cancer (IASLC) recommendations promoting liquid biopsy as a primary detection tool, a new era of research has begun. The authors aimed to study the concordance of plasma genotyping platforms against the tissue gold standard. Methods: 184 patients with non-small cell lung cancer underwent EGFR genotyping using Cobas, droplet digital polymerase chain reaction (ddPCR) and Therascreen assays from 2019–2020. Results: Of 184 cases, 70 were positive by Cobas, 51 by ddPCR and 69 by Therascreen. The sensitivity of Cobas was 97.1% and the sensitivity of ddPCR was 71%. Receiver operating characteristic analysis showed an area under the curve of 0.977 for Cobas and 0.846 for ddPCR. Conclusion: In line with the FLAURA trial of osimertinib making its way to first-line and given the IASLC recommendations, it is important to understand the attributes of these tests to initiate appropriate treatment.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nayara I. Medeiros ◽  
Juliana A. S. Gomes ◽  
Jacqueline A. Fiuza ◽  
Giovane R. Sousa ◽  
Eliane F. Almeida ◽  
...  

Abstract One of the major challenges in chronic Chagas disease is to understand the mechanisms that predict the clinical evolution from asymptomatic to severe cardiac clinical forms. Our cohort consisted of twenty-eight Chagas disease patients followed for twenty years. Plasma levels of MMP-2 and MMP-9 gelatinases and TIMPs were evaluated by multiplexed immunoassay at two points in time with an average interval of six years. MMP-2 plasma levels, but not MMP-9, increased in cardiac patients over time. TIMP-1 levels diminished in cardiac patients, while TIMP-3 dropped in asymptomatic patients in the course of the evaluated interval. An inversion of time lines was observed relative to the clinical asymptomatic and cardiac forms for MMP-2. Receiver Operating Characteristic (ROC) curve analysis identified MMP-2 as a biomarker to distinguish asymptomatic from cardiac clinical forms, while MMP-9 is a biomarker that segregates infected from non-infected patients. We have pointed out that MMP-2 and MMP-9 together can predict clinical evolution in Chagas disease. MMP-2 was suggested as a biomarker for fibrosis replacement in early remodeling and a sensitive predictor for initial changes in asymptomatic patients that may evolve into the cardiac clinical form. MMP-9 seems to be a biomarker for late fibrosis and severe cardiac remodeling in cardiac patients.


Acta Tropica ◽  
2002 ◽  
Vol 81 (1) ◽  
pp. 21-31 ◽  
Author(s):  
F.M.G Araújo ◽  
M.T Bahia ◽  
N.M Magalhães ◽  
O.A Martins-Filho ◽  
V.M Veloso ◽  
...  

2015 ◽  
Vol 8 (1) ◽  
pp. 154 ◽  
Author(s):  
Myllena F Melo ◽  
Otacilio C Moreira ◽  
Priscila Tenório ◽  
Virginia Lorena ◽  
Izaura Lorena-Rezende ◽  
...  

Author(s):  
Melissa J. Reimer-McAtee ◽  
Carolina Mejia ◽  
Taryn Clark ◽  
Jules Terle ◽  
Monica J. Pajuelo ◽  
...  

This cross-sectional study evaluated epidemiologic characteristics of persons living with HIV (PWH) coinfected with Trypanosoma cruzi in Cochabamba, Bolivia, and estimated T. cruzi parasitemia by real-time quantitative polymerase chain reaction (qPCR) in patients with and without evidence of reactivation by direct microscopy. Thirty-two of the 116 HIV patients evaluated had positive serology for T. cruzi indicative of chronic Chagas disease (27.6%). Sixteen of the 32 (50%) patients with positive serology were positive by quantitative polymerase chain reaction (qPCR), and four of the 32 (12.5%) were positive by direct microscopy. The median parasite load by qPCR in those with CD4+ < 200 was 168 parasites/mL (73-9951) compared with 28.5 parasites/mL (15–1,528) in those with CD4+ ≥ 200 (P = 0.89). There was a significant inverse relationship between the degree of parasitemia estimated by qPCR from blood clot and CD4+ count on the logarithmic scale (rsBC= –0.70, P = 0.007). The correlation between T. cruzi estimated by qPCR+ blood clot and HIV viral load was statistically significant with rsBC = 0.61, P = 0.047. Given the significant mortality of PWH and Chagas reactivation and that 57% of our patients with CD4+ counts < 200 cells/mm3 showed evidence of reactivation, we propose that screening for chronic Chagas disease be considered in PWH in regions endemic for Chagas disease and in the immigrant populations in nonendemic regions. Additionally, our study showed that PWH with advancing immunosuppression have higher levels of estimated parasitemia measured by qPCR and suggests a role for active surveillance for Chagas reactivation with consideration of treatment with antitrypanosomal therapy until immune reconstitution can be achieved.


2018 ◽  
Vol 12 (11) ◽  
pp. e0006939 ◽  
Author(s):  
Ícaro Rodrigues-dos-Santos ◽  
Myllena F. Melo ◽  
Liane de Castro ◽  
Alejandro Marcel Hasslocher-Moreno ◽  
Pedro Emmanuel A. A. do Brasil ◽  
...  

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