Proteomic Profiling Identifies MARCO in Extracellular Vesicles, as a Potential Biomarker for Leishmaniasis in HIV Co-Infection
Abstract
1. Introduction
2. Results
2.1. Enzyme-Linked Immunosorbent Assay (ELISA) Results for Antigens SPLA, rK28 and SECA
2.2. Purification and Characterization of Plasma-Derived EVs
2.3. Leishmania Proteins Identification in Patient HIV+/VL+
2.4. Human Proteins Identification in Patient HIV+VL+
2.5. Quantitative Analysis of Human Proteins
2.6. Human Derived Biomarkers of VL
3. Discussion
4. Materials and Methods
4.1. Clinical Description of the Study Patient
4.2. Cohort Design: Leishmania+HIV+ Patient, HIV+ Patients and HIV−VL− Controls
4.3. Blood Collection and Plasma Processing
4.4. Parasites and Cell Culture
4.5. Antigens
4.6. Enzyme-Linked Immunosorbent Assay (ELISA)
4.7. Roc Curve Determination
4.8. Purification of Plasma-Derived EVs by Size-Exclusion Chromatograph
4.9. Bead-Based Flow Cytometry Assay
4.10. Plasma EVs Protein Quantification
4.11. Nanoparticle Track Analysis
4.12. Electron Microscopy
4.13. Samples Preparation and Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
4.14. Quantitative Evaluation of Human Proteins
4.15. Western Blot
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sample | Collection Date | Sex | Age | Hospital | Clinical Aspects (Date Diagnostic) | Treatment | Parasitemia PCR (Copies/mL) |
---|---|---|---|---|---|---|---|
HIV+/VL+ | 16/05/19 (TP1) | M | 45 | Centro Hospitalar Universitário de São João, Porto, Portugal | HIV (2000) and VL (2013) | Lipossomal Amphotericin B and Miltefosine | 5000 |
14/01/20 (TP2) | 6500 | ||||||
30/07/20 (TP3) | 7500 | ||||||
14/01/21 (TP4) | 3000 | ||||||
29/07/21 (TP5) | 7000 |
Sample | FDR | Accession (UniProtKB) | Leishmania Locus Tag | Description | PSMs | UPs |
---|---|---|---|---|---|---|
TP1 | Medium | A4HSB7 | LINJ_04_1200 | Uncharacterized protein | 1 | 1 |
Medium | A4HUI7 | LINJ_10_0800 | Uncharacterized protein | 1 | 1 | |
TP2 | Low | A4HTG6 | LINJ_08_0160 | GPI-GlcNAc transferase complex PIG-H component conserved domain-containing protein | 1 | 1 |
TP3 | Medium | A4I7M2 | LINJ_32_0630 | Uncharacterized protein | 1 | 1 |
TP4 | Medium | A4HVH9 ** | LINJ_13_0390 | Putative RNA helicase | 1 | 1 |
TP5 | Medium | A4HVL3 | LINJ_13_0740 | Uncharacterized protein | 1 | 1 |
Low | E9AHM5 | LINJ_32_4140 | Putative GIPL galf transferase | 1 | 1 | |
Pool HIV+VL+ | High | A4HSC2 ** | LINJ_04_1250 | Actin | 72 | 1 |
High | A4I7Z7 * | LINJ_32_1910 | Superoxide dismutase | 3 | 1 | |
High | A4IA22 * | LINJ_34_2280 | Uncharacterized protein | 3 | 1 | |
High | A4I0Q2 | LINJ_24_0650 | Kinesin-like protein | 1 | 1 | |
Medium | A4I2B2 | LINJ_26_1790 | HEAT repeat-containing protein 1 | 2 | 1 | |
Medium | A4I7L3 | LINJ_32_0720 | Small ribosomal subunit protein uS4 N-terminal domain-containing protein | 4 | 1 | |
Medium | A4HW49 | LINJ_14_1140 | Protein kinase domain-containing protein | 2 | 1 | |
Medium | A4HT30 | LINJ_07_0090 | RAVE complex protein Rav1 C-terminal domain-containing protein | 4 | 1 |
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Costa, I.; Pinto, A.I.; Esteves, S.; Caldas, C.; Osório, H.; Santarém, N.; Fernandez-Becerra, C.; Cordeiro-da-Silva, A. Proteomic Profiling Identifies MARCO in Extracellular Vesicles, as a Potential Biomarker for Leishmaniasis in HIV Co-Infection. Int. J. Mol. Sci. 2025, 26, 5691. https://doi.org/10.3390/ijms26125691
Costa I, Pinto AI, Esteves S, Caldas C, Osório H, Santarém N, Fernandez-Becerra C, Cordeiro-da-Silva A. Proteomic Profiling Identifies MARCO in Extracellular Vesicles, as a Potential Biomarker for Leishmaniasis in HIV Co-Infection. International Journal of Molecular Sciences. 2025; 26(12):5691. https://doi.org/10.3390/ijms26125691
Chicago/Turabian StyleCosta, Inês, Ana Isabel Pinto, Sofia Esteves, Cátia Caldas, Hugo Osório, Nuno Santarém, Carmen Fernandez-Becerra, and Anabela Cordeiro-da-Silva. 2025. "Proteomic Profiling Identifies MARCO in Extracellular Vesicles, as a Potential Biomarker for Leishmaniasis in HIV Co-Infection" International Journal of Molecular Sciences 26, no. 12: 5691. https://doi.org/10.3390/ijms26125691
APA StyleCosta, I., Pinto, A. I., Esteves, S., Caldas, C., Osório, H., Santarém, N., Fernandez-Becerra, C., & Cordeiro-da-Silva, A. (2025). Proteomic Profiling Identifies MARCO in Extracellular Vesicles, as a Potential Biomarker for Leishmaniasis in HIV Co-Infection. International Journal of Molecular Sciences, 26(12), 5691. https://doi.org/10.3390/ijms26125691