MICA and KIR: Immunogenetic Factors Influencing Left Ventricular Systolic Dysfunction and Digestive Clinical Form of Chronic Chagas Disease.

Tissue damage observed in the clinical forms of chronic symptomatic Chagas disease seems to have a close relationship with the intensity of the inflammatory process. The objective of this study was to investigate whether the MICA (MHC class I-related chain A) and KIR (killer cell immunoglobulin-like receptors) polymorphisms are associated with the cardiac and digestive clinical forms of chronic Chagas disease. Possible influence of these genes polymorphisms on the left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas heart disease was also evaluated. This study enrolled 185 patients with positive serology for Trypanosoma cruzi classified according to the clinical form of the disease: cardiac (n=107) and digestive (n=78). Subsequently, patients with the cardiac form of the disease were sub-classified as with LVSD (n=52) and without LVSD (n=55). A control group was formed of 110 healthy individuals. Genotyping was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP). Statistical analyzes were carried out using the Chi-square test and odds ratio with 95% confidence interval was also calculated to evaluate the risk association. MICA-129 allele with high affinity for the NKG2D receptor was associated to the LVSD in patients with CCHD. The haplotype MICA*008~HLA-C*06 and the KIR2DS2-/KIR2DL2-/KIR2DL3+/C1+ combination were associated to the digestive clinical form of the disease. Our data showed that the MICA and KIR polymorphisms may exert a role in the LVSD of cardiac patients, and in digestive form of Chagas disease.

Plasma concentrations of CCL3 and CCL4 in the cardiac and digestive clinical forms of chronic Chagas disease.

The aim of this study was to investigate the plasma levels of the CCL3 and CCL4 chemokines in patients with the cardiac and digestive clinical forms of chronic Chagas disease and in cardiac patients with and without left ventricular systolic dysfunction (LVSD). Plasma samples from 75 patients were evaluated by enzyme-linked immunosorbent assay (ELISA) to confirm infection by T. cruzi. Plasma levels of the CCL3 and CCL4 chemokines were measured using Milliplex® MAP assay (Millipore). There were no significant differences in the levels of CCL3 and CCL4 between patients with the digestive and cardiac clinical forms of Chagas disease. Moreover, no significant differences were found between patients without LVSD and those with LVSD. Higher CCL3 and CCL4 plasma levels were found in patients with LVSD compared to those with the digestive form of the disease. The CCL3 and CCL4 chemokines might not be involved in differential susceptibility to the digestive and cardiac clinical forms of chronic Chagas disease, and it seems they do not influence the development of LVSD.

ABO, Secretor and Lewis histo-blood group systems influence the digestive form of Chagas disease.

Chagas disease, caused by Trypanosoma cruzi, can affect the heart, esophagus and colon. The reasons that some patients develop different clinical forms or remain asymptomatic are unclear. It is believed that tissue immunogenetic markers influence the tropism of T. cruzi for different organs. ABO, Secretor and Lewis histo-blood group systems express a variety of tissue carbohydrate antigens that influence the susceptibility or resistance to diseases. This study aimed to examine the association of ABO, secretor and Lewis histo-blood systems with the clinical forms of Chagas disease. We enrolled 339 consecutive adult patients with chronic Chagas disease regardless of gender (cardiomyopathy: n=154; megaesophagus: n=119; megacolon: n=66). The control group was composed by 488 healthy blood donors. IgG anti-T. cruzi antibodies were detected by ELISA. ABO and Lewis phenotypes were defined by standard hemagglutination tests. Secretor (FUT2) and Lewis (FUT3) genotypes, determined by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), were used to infer the correct histo-blood group antigens expressed in the gastrointestinal tract. The proportions between groups were compared using the χ2 test with Yates correction and Fisher's exact test and the Odds Ratio (OR) and 95% Confidence Interval (95% CI) were calculated. An alpha error of 5% was considered significant with p-values <0.05 being corrected for multiple comparisons (pc). No statistically significant differences were found for the ABO (X2: 2.635; p-value=0.451), Secretor (X2: 0.056; p-value=0.812) or Lewis (X2: 2.092; p-value=0.351) histo-blood group phenotypes between patients and controls. However, B plus AB Secretor phenotypes were prevalent in pooled data from megaesophagus and megacolon patients (OR: 5.381; 95% CI: 1.230-23.529; p-value=0.011; pc=0.022) in comparison to A plus O Secretor phenotypes. The tissue antigen variability resulting from the combined action of ABO and Secretor histo-blood systems is associated with the digestive forms of Chagas disease.

Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.