Serological reactivity against T. cruzi-derived antigens: Evaluation of their suitability for the assessment of response to treatment in chronic Chagas disease.

NHEPACHA Study Group

doi:10.1016/j.actatropica.2021.105990

Serological reactivity against T. cruzi-derived antigens: Evaluation of their suitability for the assessment of response to treatment in chronic Chagas disease.

NHEPACHA Study Group

Faculty of Exact and Natural Sciences

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects more than 6 million people worldwide. Following a mostly asymptomatic acute phase, the disease progresses to a long-lasting chronic phase throughout which life-threatening disorders to the heart and/or gastrointestinal tract will manifest in about 30% of those chronically infected. During the chronic phase, the parasitemia is low and intermittent, while a high level of anti-T. cruzi antibodies persist for years. These two features hamper post-chemotherapeutic follow-up of patients with the tools available. The lack of biomarkers for timely assessment of therapeutic response discourages a greater use of the two available anti-parasitic drugs, and complicates the evaluation of new drugs in clinical trials. Herein, we investigated in a blinded case-control study the serological reactivity over time of a group of parasite-derived antigens to potentially address follow up of T. cruzi chronically infected subjects after treatment. We tested PFR2, KMP11, HSP70, 3973, F29 and the InfYnity multiplexed antigenic array, by means of serological assays on a multi-national retrospective collection of samples. Some of the antigens exhibited promising results, underscoring the need for further studies to determine their potential role as treatment response biomarkers.

Original language	English
Article number	105990
Journal	Acta Tropica
Volume	221
DOIs	https://doi.org/10.1016/j.actatropica.2021.105990
State	Published - Sep 2021

Bibliographical note

Publisher Copyright:
© 2021

Funding

ISGlobal authors thanks the support by the Departament d'Universitats i Recerca de la Generalitat de Catalunya, Spain (AGAUR; 2017SGR00924), funding by the Instituto de Salud Carlos III project PI18/01054 and RICET Network for Cooperative Research in Tropical Diseases (RD12/0018/0010) and FEDER, and the support to ISGlobal from the Spanish Ministry of Science Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019–2023″ Program (CEX2018–000806-S), and from the Generalitat de Catalunya through the CERCA Program. IPBLN work was financially supported by grants SAF2016–81003-R and SAF2016–80998-R from the Programa Estatal I + D + i (MINECO) and ISCIII RICET (RD16/0027/0005) and FEDER. MJP research is supported by the Ministry of Health, Government of Catalunya (PERIS 2016–2010 SLT008/18/00132). TAJ thanks the support of Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq/ 313011/2018–4) and Fundação Oswaldo Cruz/MS (25380.001603/2017–89). Authors also thank Drugs for Neglected Diseases initiative and Fundacion Mundo Sano for financial support. For this project, DNDi received financial support from the following donors: UK Aid, UK; Directorate-General for International Cooperation (DGIS), The Netherlands; Swiss Agency for Development and Cooperation (SDC), Switzerland; Médecins Sans Frontières (MSF), International. We thank Dr. A. Egui, Dr A. Fernández-Villegas and A. López-Barajas from IPBLN[sbnd]CSIC (Granada, Spain), Carme Subirá from ISGlobal (Barcelona, Spain), and Suelene B. N. Tavares from Hospital das Clínicas (Goiás, Brazil) for their technical assistance. We also want to thank Dr. B. Carrilero from Hospital Virgen de la Arrixaca (Murcia, Spain), Dr. Dayse E.C. de Oliveira from Hospital das Clínicas (Goiás, Brazil), and Dr. Raúl Chadi from Hospital General de Agudos “Dr. I. Pirovano” for their clinical follow up of patients. ISGlobal authors thanks the support by the Departament d'Universitats i Recerca de la Generalitat de Catalunya, Spain (AGAUR; 2017SGR00924), funding by the Instituto de Salud Carlos III project PI18/01054 and RICET Network for Cooperative Research in Tropical Diseases (RD12/0018/0010) and FEDER, and the support to ISGlobal from the Spanish Ministry of Science Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019–2023″ Program (CEX2018–000806-S), and from the Generalitat de Catalunya through the CERCA Program. IPBLN work was financially supported by grants SAF2016–81003-R and SAF2016–80998-R from the Programa Estatal I + D + i (MINECO) and ISCIII RICET (RD16/0027/0005) and FEDER. MJP research is supported by the Ministry of Health, Government of Catalunya (PERIS 2016–2010 SLT008/18/00132). TAJ thanks the support of Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq/ 313011/2018–4) and Fundação Oswaldo Cruz/MS (25380.001603/2017–89). Authors also thank Drugs for Neglected Diseases initiative and Fundacion Mundo Sano for financial support. For this project, DNDi received financial support from the following donors: UK Aid, UK; Directorate-General for International Cooperation (DGIS), The Netherlands; Swiss Agency for Development and Cooperation (SDC), Switzerland; Médecins Sans Frontières (MSF), International. The donors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funders	Funder number
Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico
DGIS
Directorate-General for International Cooperation
Hospital General de Agudos
Hospital Virgen de la Arrixaca
Hospital das Clínicas
IPBLN
ISCIII RICET	RD16/0027/0005
Ministry of Health, Government of Catalunya	PERIS 2016–2010 SLT008/18/00132
RICET	RD12/0018/0010
Médecins Sans Frontières
Direktion für Entwicklung und Zusammenarbeit
Ministerio de Ciencia, Innovación y Universidades	CEX2018–000806-S
Generalitat de Catalunya	SAF2016–80998-R, SAF2016–81003-R
Federación Española de Enfermedades Raras
Agència de Gestió d'Ajuts Universitaris i de Recerca	2017SGR00924
Ministerio de Economía y Competitividad
Consejo Superior de Investigaciones Científicas
Conselho Nacional de Desenvolvimento Científico e Tecnológico	/ 313011/2018–4
Instituto de Salud Carlos III	PI18/01054
Fundação Oswaldo Cruz	25380.001603/2017–89
Fundación Mundo Sano

Keywords

3973
Antigens
Chagas disease
Chemotherapy response
Chronic infection
F29
HSP70
InfYnity multiplexed ELISA
KMP11
PFR2
Trypanosoma cruzi

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10.1016/j.actatropica.2021.105990

Cite this

@article{6e0f6008896c4653b5a62d7d1c0284bb,

title = "Serological reactivity against T. cruzi-derived antigens: Evaluation of their suitability for the assessment of response to treatment in chronic Chagas disease.",

abstract = "Chagas disease, caused by the protozoan Trypanosoma cruzi, affects more than 6 million people worldwide. Following a mostly asymptomatic acute phase, the disease progresses to a long-lasting chronic phase throughout which life-threatening disorders to the heart and/or gastrointestinal tract will manifest in about 30% of those chronically infected. During the chronic phase, the parasitemia is low and intermittent, while a high level of anti-T. cruzi antibodies persist for years. These two features hamper post-chemotherapeutic follow-up of patients with the tools available. The lack of biomarkers for timely assessment of therapeutic response discourages a greater use of the two available anti-parasitic drugs, and complicates the evaluation of new drugs in clinical trials. Herein, we investigated in a blinded case-control study the serological reactivity over time of a group of parasite-derived antigens to potentially address follow up of T. cruzi chronically infected subjects after treatment. We tested PFR2, KMP11, HSP70, 3973, F29 and the InfYnity multiplexed antigenic array, by means of serological assays on a multi-national retrospective collection of samples. Some of the antigens exhibited promising results, underscoring the need for further studies to determine their potential role as treatment response biomarkers.",

keywords = "3973, Antigens, Chagas disease, Chemotherapy response, Chronic infection, F29, HSP70, InfYnity multiplexed ELISA, KMP11, PFR2, Trypanosoma cruzi",

author = "{NHEPACHA Study Group} and Julio Alonso-Padilla and L{\'o}pez, {Manuel Carlos} and M{\'o}nica Esteva and Maan Zrein and Aina Casellas and Inmaculada G{\'o}mez and Elodie Granjon and Susana M{\'e}ndez and Celia Ben{\'i}tez and Ruiz, {Andres Mariano} and Sergi Sanz and Joaquim Gasc{\'o}n and Thomas, {M. Carmen} and Pinazo, {Maria Jesus} and Marcelo Abril and {de Noya}, {Belkisyol{\'e} Alarc{\'o}n} and Jorge, {Tania Araujo} and Eric Chatelain and Grijalva, {Mario J.} and Felipe Guhl and Hasslocher-Moreno, {Alejandro Marcel} and Luquetti, {Alejandro O.} and Oscar Noya and Ramsey, {Janine M.} and Isabela Ribeiro and Longhi, {Silvia A.} and Schijman, {Alejandro G.} and Sergio Sosa-Estani and Faustino Torrico and Rodolfo Viotti",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = sep,

doi = "10.1016/j.actatropica.2021.105990",

language = "English",

volume = "221",

journal = "Acta Tropica",

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T2 - Evaluation of their suitability for the assessment of response to treatment in chronic Chagas disease.

AU - NHEPACHA Study Group

AU - Alonso-Padilla, Julio

AU - López, Manuel Carlos

AU - Esteva, Mónica

AU - Zrein, Maan

AU - Casellas, Aina

AU - Gómez, Inmaculada

AU - Granjon, Elodie

AU - Méndez, Susana

AU - Benítez, Celia

AU - Ruiz, Andres Mariano

AU - Sanz, Sergi

AU - Gascón, Joaquim

AU - Thomas, M. Carmen

AU - Pinazo, Maria Jesus

AU - Abril, Marcelo

AU - de Noya, Belkisyolé Alarcón

AU - Jorge, Tania Araujo

AU - Chatelain, Eric

AU - Grijalva, Mario J.

AU - Guhl, Felipe

AU - Hasslocher-Moreno, Alejandro Marcel

AU - Luquetti, Alejandro O.

AU - Noya, Oscar

AU - Ramsey, Janine M.

AU - Ribeiro, Isabela

AU - Longhi, Silvia A.

AU - Schijman, Alejandro G.

AU - Sosa-Estani, Sergio

AU - Torrico, Faustino

AU - Viotti, Rodolfo

PY - 2021/9

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KW - Chronic infection

KW - F29

KW - HSP70

KW - InfYnity multiplexed ELISA

KW - KMP11

KW - PFR2

KW - Trypanosoma cruzi

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JO - Acta Tropica

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M1 - 105990

ER -

Serological reactivity against T. cruzi-derived antigens: Evaluation of their suitability for the assessment of response to treatment in chronic Chagas disease.

Abstract

Bibliographical note

Funding

Keywords

Access to Document

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