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. 2024 Feb 27;110(4):669-676.
doi: 10.4269/ajtmh.23-0652. Print 2024 Apr 3.

IgG Isotypes Targeting a Recombinant Chimeric Protein of Trypanosoma cruzi in Different Clinical Presentations of Chronic Chagas Disease

Isabela Machado Serrano  1   2 , Gilmar Ribeiro  1   3 , Ronnei Silva Santos  4 , Jaqueline Silva Cruz  1 , Fernanda Cardoso Lanza  1 , Emily Ferreira Dos Santos  2 , Márcio Cerqueira de Almeida  1 , Jorgana Fernanda de Souza Soares  4 , Alejandro Ostermayer Luquetti  5 , Paola Alejandra Fiorani Celedon  6 , Nilson Ivo Tonin Zanchin  3   7 , Fred Luciano Neves Santos  2   3 , Mitermayer Galvão Dos Reis  1   3   4   8
Affiliations

IgG Isotypes Targeting a Recombinant Chimeric Protein of Trypanosoma cruzi in Different Clinical Presentations of Chronic Chagas Disease

Isabela Machado Serrano et al. Am J Trop Med Hyg. .

Abstract

Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi, which leads to a spectrum of clinical presentations that range from asymptomatic to severe cardiac involvement. The host immune response plays a pivotal role in disease progression. Ig isotypes may contribute to disease pathogenesis. Investigating these components can provide insights into the immunopathogenic mechanisms underlying CD. This cross-sectional study aims to establish a correlation between the Ig profile of individuals infected with T. cruzi with the clinical forms of chronic CD. Serum samples were collected from partner institutions in different states of Brazil. Individuals diagnosed with chronic CD were categorized based on the clinical form of the disease. The indirect ELISA method using the recombinant chimeric Molecular Biology Institute of Paraná membrane protein 8.4 as the antigen was used to determine the Ig profile, including total IgG, IgG1, IgG2, IgG3, and IgG4. Ninety-seven serum samples from patients classified as negative (NEG, n = 38), indeterminate (IND, n = 24), mild cardiac (MC, n = 20), and severe cardiac (SC, n = 15) forms were analyzed. IgG1 exhibited greater levels compared with the other isotypes, showing a significant difference between the MC and IND groups. IgG3 levels were greater in individuals from the MC group compared with the SC group. IgG1 and IgG3 isotypes can serve as biomarkers to evaluate the progression of CD because they exhibit variations across clinical groups. Additional longitudinal studies are necessary to explore the relationship between antibody kinetics and the development of tissue damage.

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Conflict of interest statement

Disclosure: This study received approval from the Institutional Review Board (IRB) for Human Research at the Gonçalo Moniz Institute, Oswaldo Cruz Foundation–Bahia, Salvador, Brazil (protocol no. 67809417.0.0000.0040). Samples were obtained from various reference laboratories, including the Reference Laboratory for Chagas Disease, Oswaldo Cruz Foundation–Pernambuco from 2010 to 2015; the Laboratory for Chagas Disease Research, Federal University of Goiás, Brazil, from 2000 to 2015; the Foundation for Hematology and Hemotherapy of Bahia from 2020 to 2022; and the Foundation for Hematology and Hemotherapy of Pernambuco from 2012 to 2015. To safeguard patient confidentiality, the IRB mandated that all samples be coded to ensure anonymity and to eliminate the need for verbal or written consent. As a result, all patient data were fully anonymized and inaccessible to researchers. The funders had no influence on the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Figures

Figure 1.
Figure 1.
Geographic location of sample collection sites in this study. Source base layer and credit base layer: https://data.humdata.org/ published under creative commons attribution for intergovernmental organizations and https://data.humdata.org/dataset/geoboundaries-admin-boundaries-for-brazil. Reprinted with permission.
Figure 2.
Figure 2.
Graphical analysis of the reactivity index (RI) obtained with serum samples of Trypanosoma cruzi–positive and T. cruzi–negative (NEG) samples against total IgG against the T. cruzi IBMP-8.5 antigen. The cutoff value is RI = 1.0. The shaded area represents the gray zone (RI, 1.0 ± 0.10). IND = samples from T. cruzi–positive individuals with indeterminate form; IQR = interquartile range; MC = samples from T. cruzi–positive individuals with mild cardiac form; SC = samples from T. cruzi–positive individuals with severe cardiac form.
Figure 3.
Figure 3.
Graphical analysis of the reactivity index (RI) obtained with serum samples of Trypanosoma cruzi–positive and T. cruzi–negative (NEG) samples against IgG isotypes against the T. cruzi IBMP-8.4 antigen. The cutoff value is RI = 1.0. The shaded area represents the gray zone (RI, 1.0 ± 0.10). IND = samples from T. cruzi–positive individuals with indeterminate form; IQR = interquartile range; MC = samples from T. cruzi–positive individuals with mild cardiac form; SC = samples from T. cruzi–positive individuals with severe cardiac form.
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