Dataset Information

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease.

ABSTRACT: Galectin-3, a ?-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated.The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease.Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene.For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease.Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease.

SUBMITTER: Cruz Gda S

PROVIDER: S-EPMC4651405 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease.

Cruz Gabriela da Silva Gda S Angelo Ana Luiza Dias AL Larocca Ticiana Ferreira TF Macedo Carolina Thé CT Noya-Rabelo Márcia M Correia Luís Claudio Lemos LC Torreão Jorge Andion JA Souza Bruno Solano de Freitas BS Santos Ricardo Ribeiro Dos RR Soares Milena Botelho Pereira MB

Arquivos brasileiros de cardiologia 20150825 5

<h4>Background</h4>Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relation ...[more]

PMID: 26312551

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Project description:Infection by the Trypanosoma cruzi parasite causes Chagas disease and triggers multiple immune mechanisms in the host to combat the pathogen. Chagas disease has a variable clinical presentation and progression, producing in the chronic phase a fragile balance between the host immune response and parasite replication that keeps patients in a clinically silent asymptomatic stage for years. Since the parasite is intracellular and replicates within cells, the cell-mediated response of the host adaptive immunity plays a critical role. This function is mainly orchestrated by T lymphocytes, which recognize parasite antigens and promote specific functions to control the infection. However, little is known about the immunological markers associated with this asymptomatic stage of the disease. In this large-scale analysis, the differential expression of 106 immune system-related genes has been analyzed using high-throughput qPCR in T. cruzi antigen-stimulated PBMC from chronic Chagas disease patients with indeterminate form (IND) and healthy donors (HD) from endemic and non-endemic areas of Chagas disease. This analysis revealed that there were no differences in the expression level of most genes under study between healthy donors from endemic and non-endemic areas determined by PCA and differential gene expression analysis. Instead, PCA revealed the existence of different expression profiles between IND patients and HD (p < 0.0001), dependent on the 32 genes included in PC1. Differential gene expression analysis also revealed 23 upregulated genes (expression fold change > 2) and 11 downregulated genes (expression fold change < 0.5) in IND patients versus HD. Enrichment analysis showed that several upregulated genes in IND patients participate in relevant immunological pathways such as antigen-dependent B cell activation, stress induction of HSP regulation, NO2-dependent IL12 pathway in NK cells, and cytokine-inflammatory response. The antigen-specific differential gene expression profile detected in these patients and the relevant immunological pathways that seem to be activated could represent potential biomarkers of the asymptomatic form of Chagas disease, helpful to diagnosis and infection control.

Project description:We had formerly demonstrated that subjects chronically infected with Trypanosoma cruzi show impaired T cell responses closely linked with a process of T cell exhaustion. Recently, the expression of several inhibitory receptors has been associated with T cell dysfunction and exhaustion. In this study, we have examined the expression of the cytotoxic T lymphocyte antigen 4 (CTLA-4) and the leukocyte immunoglobulin like receptor 1 (LIR-1) by peripheral T. cruzi antigen-responsive IFN-gamma (IFN-?)-producing and total T cells from chronically T. cruzi-infected subjects with different clinical forms of the disease. CTAL-4 expression was also evaluated in heart tissue sections from subjects with severe myocarditis. The majority of IFN-?-producing CD4(+) T cells responsive to a parasite lysate preparation were found to express CTLA-4 but considerably lower frequencies express LIR-1, irrespective of the clinical status of the donor. Conversely, few IFN-?-producing T cells responsive to tetanus and diphtheria toxoids expressed CTLA-4 and LIR-1. Polyclonal stimulation with anti-CD3 antibodies induced higher frequencies of CD4(+)CTAL-4(+) T cells in patients with severe heart disease than in asymptomatic subjects. Ligation of CTLA-4 and LIR-1 with their agonistic antibodies, in vitro, reduces IFN-? production. Conversely, CTLA-4 blockade did not improved IFN-? production in response to T. cruzi antigens. Subjects with chronic T. cruzi infection had increased numbers of CD4(+)LIR-1(+) among total peripheral blood mononuclear cells, relative to uninfected individuals and these numbers decreased after treatment with benznidazole. CTLA-4 was also expressed by CD3(+) T lymphocytes infiltrating heart tissues from chronically infected subjects with severe myocarditis. These findings support the conclusion that persistent infection with T. cruzi leads to the upregulation of inhibitory receptors which could alter parasite specific T cell responses in the chronic phase of Chagas disease.

Dataset Information

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease.

Publications

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease.

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