Browsing by Autor "Janine M. Ramsey"

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A <i>Trypanosoma cruzi</i> Antigen and Epitope Atlas: deep characterization of antibody specificities in Chagas Disease patients across the Americas
(2022) Alejandro D. Ricci; Leonel Bracco; Janine M. Ramsey; Melissa S. Nolan; Mary K. Lynn; Jaime Altcheh; Griselda Ballering; Faustino Torrico; Norival Kesper; Juan Carlos Villar
ABSTRACT During an infection, the immune system produces pathogen-specific antibodies. With time, these antibody repertoires become specific to the history of infections and represent a rich source of diagnostic markers. However, the specificities of these antibodies are mostly unknown. Here, using high-density peptide arrays we examined the specificities of human antibody repertoires of Chagas disease patients. Chagas disease is a neglected disease caused by Trypanosoma cruzi, a protozoan parasite that evades immune mediated elimination and mounts long-lasting chronic infections. We describe here the first proteome-wide search for antigens and epitopes and their seroprevalence at the individual level and across human populations. In a first discovery screening of 2.84 million short peptides spanning two T. cruzi proteomes we found 3,868 distinct antigenic protein regions. Further analysis of repertoires from 71 individuals provided information on their seroprevalence and showed a large fraction of private epitopes of low seroprevalence (<20%), and novel high seroprevalence antigens. Using single-residue mutagenesis we found the core epitopes required for antibody binding for 232 of these epitopes. These datasets enable the study of the Chagas antibody repertoire at an unprecedented depth and granularity, while also providing a rich source of novel serological biomarkers. IMPACT STATEMENT This work reveals the diversity and extent of antibody specificities in Chagas Disease and provides a wealth of well-defined antigenic markers for diagnosis and development of serological applications for this neglected infectious disease.
A guide for the generation of repositories of clinical samples for research on Chagas disease
(Public Library of Science, 2024) Nieves Martínez-Peinado; Juan Carlos Gabaldón-Figueira; Roberto Rodrigues Ferreira; M. Carmen Thomas; Manuel Carlos López; Tânia Cremonini de Araújo-Jorge; Belkisyolé Alarcón de Noya; Soledad Berón; Janine M. Ramsey; Irene Losada
Chagas disease, caused by the parasite Trypanosoma cruzi, affects over 6 million people, mainly in Latin America. Two different clinical phases, acute and chronic, are recognised. Currently, 2 anti-parasitic drugs are available to treat the disease (nifurtimox and benznidazole), but diagnostic methods require of a relatively complex infrastructure and trained personnel, limiting its widespread use in endemic areas, and the access of patients to treatment. New diagnostic methods, such as rapid tests (RDTs) to diagnose chronic Chagas disease, or loop-mediated isothermal amplification (LAMP), to detect acute infections, represent valuable alternatives, but the parasite's remarkable genetic diversity might make its implementation difficult. Furthermore, determining the efficacy of Chagas disease treatment is complicated, given the slow reversion of serological anti-T. cruzi antibody reactivity, which may even take decades to occur. New biomarkers to evaluate early therapeutic efficacy, as well as diagnostic tests able to detect the wide variety of circulating genotypes, are therefore, urgently required. To carry out studies that address these needs, high-quality and traceable samples from T. cruzi-infected individuals with different geographical backgrounds, along with associated clinical and epidemiological data, are necessary. This work describes the framework for the creation of such repositories, following standardised and uniform protocols, and considering the ethical, technical, and logistic aspects of the process. The manual can be adapted according to the resources of each laboratory, to guarantee that samples are obtained in a reproducible way, favouring the exchange of data among different work groups, and their generalizable evaluation and analysis. The main objective of this is to accelerate the development of new diagnostic methods and the identification of biomarkers for Chagas disease.
Deep serological profiling of the Trypanosoma cruzi TSSA antigen reveals different epitopes and modes of recognition by Chagas disease patients
(Public Library of Science, 2023) Guadalupe Romer; Leonel Bracco; Alejandro D. Ricci; Virginia Balouz; Luisa Berná; Juan Carlos Villar; Janine M. Ramsey; Melissa S. Nolan; Faustino Torrico; Norival Kesper
Overall, our findings shed new light into TSSA evolution, epitope landscape and modes of recognition by Chagas disease patients; and have practical implications for the design and/or evaluation of T. cruzi serotyping strategies.
The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas
(Nature Portfolio, 2023) Alejandro D. Ricci; Leonel Bracco; Emir Salas‐Sarduy; Janine M. Ramsey; Melissa S. Nolan; Mary K. Lynn; Jaime Altcheh; Griselda Ballering; Faustino Torrico; Norival Kesper
During an infection the immune system produces pathogen-specific antibodies. These antibody repertoires become specific to the history of infections and represent a rich source of diagnostic markers. However, the specificities of these antibodies are mostly unknown. Here, using high-density peptide arrays we examined the human antibody repertoires of Chagas disease patients. Chagas disease is a neglected disease caused by Trypanosoma cruzi, a protozoan parasite that evades immune mediated elimination and mounts long-lasting chronic infections. We describe a proteome-wide search for antigens, characterised their linear epitopes, and show their reactivity on 71 individuals from diverse human populations. Using single-residue mutagenesis we revealed the core functional residues for 232 of these epitopes. Finally, we show the diagnostic performance of identified antigens on challenging samples. These datasets enable the study of the Chagas antibody repertoire at an unprecedented depth and granularity, while also providing a rich source of serological biomarkers.
Towards a Paradigm Shift in the Treatment of Chronic Chagas Disease
(American Society for Microbiology, 2013) Rodolfo Viotti; Belkisyolé Alarcón de Noya; Tânia Cremonini de Araújo-Jorge; Mario J. Grijalva; Felipe Guhl; Manuel Carlos López; Janine M. Ramsey; Isabela Ribeiro; Alejandro G. Schijman; Sergio Sosa‐Estáni
Treatment for Chagas disease with currently available medications is recommended universally only for acute cases (all ages) and for children up to 14 years old. The World Health Organization, however, also recommends specific antiparasite treatment for all chronic-phase Trypanosoma cruzi-infected individuals, even though in current medical practice this remains controversial, and most physicians only prescribe palliative treatment for adult Chagas patients with dilated cardiomyopathy. The present opinion, prepared by members of the NHEPACHA network (Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas/New Tools for the Diagnosis and Evaluation of Chagas Disease Patients), reviews the paradigm shift based on clinical and immunological evidence and argues in favor of antiparasitic treatment for all chronic patients. We review the tools needed to monitor therapeutic efficacy and the potential criteria for evaluation of treatment efficacy beyond parasitological cure. Etiological treatment should now be mandatory for all adult chronic Chagas disease patients.