ORIGINAL RESEARCH article
Front. Immunol.
Sec. Parasite Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1646335
This article is part of the Research TopicThe Impact of Proteomics on Understanding Inflammatory and Infectious DiseasesView all 6 articles
Proteomics of plasma-derived extracellular vesicles from human patients identifies biomarkers for monitoring visceral leishmaniasis therapy
Provisionally accepted
Ana Torres1,2
Ana Montero Calle3
Marina Lozano-Rendal1
Carmen Sánchez1
Lorena Bernardo1,2*
Jose Carlos Solana1,2*
Juan Victor San Martin2,4
Rodrigo Barderas3,5
Javier Moreno1,2
Eugenia Carrillo1,2- 1WHO Collaborating Centre for Leishmaniasis, Spanish National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain
- 2Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
- 3Chronic Disease Program (UFIEC), Instituto de Salud Carlos III, Majadahonda, Spain
- 4Hospital Universitario de Fuenlabrada, Dept. of Infectious Diseases, Internal Medicine, Fuenlabrada, Spain
- 5Centro de Investigacion Biomedica en Red Fragilidad y Envejecimiento Saludable, Madrid, Spain
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Introduction: The most severe form of leishmaniasis, visceral leishmaniasis (VL), lacks standardized validated early predictors of treatment success or relapse. To distinguish between active infection and successful treatment, we searched for protein biomarkers in plasma-derived extracellular vesicles (EVs). Methods: The proteomic profiles of EVs from immunocompetent patients with active VL (n=12) or 1, 3, or 6 months after completing a standard treatment regimen (n=12 each) were analyzed by LC-MS/MS. Six candidate biomarkers were further tested by ELISA in whole plasma. Results: 132 human proteins were differentially expressed in active VL-versus successfully treated patients. Pathway analysis identified pathogenic mechanisms associated with VL and pathways related to effective cure. SAA is directly measurable in whole plasma and exhibits differential expression levels, emerging as a promising, easily measurable, non-specific prognostic biomarker for patient management. Remarkably, we also identified Leishmania spp. proteins in EV samples, indicating a new source of parasite biomarkers in human samples. Conclusion: Plasma EVs contain protein biomarkers that can be used to monitor the response to treatment, some of which are detectable in whole plasma after 1 month of treatment. Our study also provides a proteomic landscape of plasma EVs involved in VL, offering insight into the pathogenesis of this complex disease.
Keywords: extracellular vesicles, Proteomics, Plasma, biomarkers, Visceral leishmaniasis, Cure, Patients
Received: 13 Jun 2025; Accepted: 21 Aug 2025.
Copyright: © 2025 Torres, Montero Calle, Lozano-Rendal, Sánchez, Bernardo, Solana, San Martin, Barderas, Moreno and Carrillo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lorena Bernardo, WHO Collaborating Centre for Leishmaniasis, Spanish National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain
Jose Carlos Solana, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
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