Variantes genéticas de CCR5 e concentrações plasmáticas das quimiocinas CCL3 e CCL4 na doença de Chagas crônica

Abstract

Chagas disease is a disease resulting from infection by the protozoan Trypanosoma cruzi. The clinical manifestations of this disease are represented by the following forms: indeterminate, cardiac, digestive or mixed. The immune response plays an important role in determining the outcome of infection. The CC chemokine receptor 5 (CCR5) and chemokines CCL3 and CCL4 (ligands of this receptor) are involved in the migration of leukocytes to sites of inflammation. Objectives: The aim of this study was to evaluate if the CCR5Δ32 (rs333) and CCR5 59029 A/G (rs1799987) polymorphisms of the CCR5 gene and plasma concentrations of chemokines CCL3 and CCL4 are associated with different clinical forms of chronic Chagas disease and with left ventricular systolic dysfunction. Methods: The study included 277 patients, 109 with the digestive form of the disease and 168 with the cardiac form. The control group comprised 172 blood donors with negative serology for T. cruzi. Infection by T. cruzi was confirmed by ELISA. The polymorphisms were identified by PCR and PCR-RFLP. The chemokines levels were measured using a Milliplex® MAP multiplex assay (Millipore). The unpaired t test was used to compare continuous variables. Chi-square, the Student's t test or Mann-Whitney test were used to compare the results. Results: The genotypes and alleles of the CCR5Δ32 and CCR5 59029 A/G polymorphisms did not differ between the patients with Chronic Chagas heart disease with and without left ventricular systolic dysfunction. There was a higher frequency of the AA genotype in patients with Chronic Chagas heart disease, as well as high frequency of AG genotype in patients with the digestive form. There were no differences in the concentrations of CCL3 and CCL4 among patients with digestive and heart disease, as well as in patients with normal left ventricular systolic function and dysfunction. The plasma concentrations of both CCL3 and CCL4 were greater in patients with left ventricular systolic dysfunction than in those with the digestive form. Conclusions: The CCR5Δ32 (rs333) and CCR5 59029 A/G (rs1799987) polymorphisms had no relationship with left ventricular systolic dysfunction in patients with chronic Chagas' heart disease. The CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease. The results of this study show the involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different clinical forms of chronic Chagas disease in this study population. Plasma concentrations of CCL3 and CCL4 may not be involved in the differential susceptibility to clinical forms of chronic Chagas disease, as well as in the development of left ventricular systolic dysfunction. In these patients, increased inflammatory activity dependent CCL3 and CCL4 can occur in relation to the digestive form of the disease.