Frequency distribution of XbaIG > T and HaeIIIT > C GLUT1 polymorphisms among different Brazilian ethnic groups.

GLUT is the major glucose transporter in mammalian cells. Single nucleotide polymorphisms (SNP) at GLUT1 promoter and regulatory regions have been associated to the risk of developing nephropathy in different type 1 and type 2 diabetic populations. It has been demonstrated that differences in allelic and genotypic frequencies of GLUT1 gene (SLC2A1) polymorphisms occur among different populations. Therefore, ethnic differences in distribution of GLUT1 gene polymorphisms may be an important factor in determining gene-disease association. In this study, we investigated the XbaIG > T and HaeIIIT > C polymorphisms in six different Brazilian populations: 102 individuals from Salvador population (Northern Brazil), 56 European descendants from Joinville (South Brazil), 85 Indians from Tiryió tribe (North Brazil) and 127 samples from Southern Brazil: 44 from European descendants, 42 from African descendants and 41 from Japanese descendants. Genotype frequencies from both sites did not differ significantly from those expected under the Hardy-Weinberg equilibrium. We verified that the allele frequencies of both polymorphisms were heterogeneous in these six Brazilian ethnic groups.

Fas 670 promoter polymorphism is associated to susceptibility, clinical presentation, and survival in adult T cell leukemia.

Fas (TNFRSF6/Apo-1/CD95) is a type I transmembrane receptor, which mediates apoptosis. Fas gene mutations, aberrant transcripts, and abundant expression of Fas have been reported in adult T cell leukemia (ATL). To further elucidate the role of Fas in ATL pathogenesis, we investigated whether the -670 FAS promoter A/G polymorphism (STAT1-binding site) might contribute to susceptibility and clinical outcome in ATL. Thirty-one patients with ATL, 33 healthy, human T lymphotropic virus type 1-infected individuals, and 70 healthy, uninfected controls were genotyped for the FAS -670 polymorphism by PCR-restriction fragment-length polymorphism. The AA genotype was significantly over-represented in ATL patients in comparison with healthy controls (P=0.006), as well as asymptomatics (P=0.037), corresponding to an odds ratio (OR) of 3.79 [95% confidence intervals (CI; 1.28-11.41)] and 4.58 [95% CI (1.13-20.03)], respectively. The AA group also comprised significantly more aggressive (acute and lymphoma) clinical subtypes [P=0.012; OR=8.40; 95% CI (1.60-44.12)]. In addition, we observed a statistically significant association between GG genotype and survival (log rank test, P=0.032). Finally, IFN-gamma-induced but not basal FAS mRNA levels were increased significantly (P=0.049) in PBMCs from AA versus GG individuals, demonstrating the IFN-dependent functionality of the -670 polymorphism. In conclusion, our results demonstrate that a functional Fas promoter polymorphism is significantly associated to susceptibility, clinical manifestation, and survival in ATL.

Ethnic differences in the distribution of interleukin-6 polymorphisms among three Brazilian ethnic groups.

Polymorphisms in the interleukin-6 promoter region have been associated with diseases. In this study we investigated the -634G/C and -174G/C IL-6 promoter polymorphisms in three Brazilian ethnic groups. We verified that the allele frequencies of the two polymorphisms and haplotype frequencies varied significantly between the populations.

HTLV-1 modifies the clinical and immunological response to schistosomiasis.

The immunological response in HTLV-1 infected individuals is characterized by a prominent Type-1 cytokine response with high production of IFN-gamma and TNF-alpha. In contrast, helminthic infections and in particular chronic schistosomiasis are associated with a predominant production of IL-4, IL-5, IL-10 and IL-13. Liver fibrosis is the main pathological finding in schistosomiasis that occurs after many years of infection. This pathology is T cell dependent but the immune response mechanisms are not completely understood. The North-east region of Brazil is endemic for both HTLV-1 and schistosomiasis. In the present study the immune response, clinical severity, and therapeutic response to praziquantel of patients with schistosomiasis coinfected with HTLV-1 were compared with patients infected only with S. mansoni. Patients with HTLV-1 and S. mansoni had lower levels of IL-5 (P < 0.05) and higher levels of IFN-gamma (P < 0.05) in cultures stimulated with S. mansoni antigen and decreased S. mansoni antigen specific IgE levels when compared with patients with schistosomiasis without HTLV-1 coinfection. Liver fibrosis was mild in all HTLV-1 coinfected patients and efficacy of praziquantel was lower in patients dually infected than in patients infected only with S. mansoni.

Influence of human T-cell lymphocytotropic virus type 1 infection on serologic and skin tests for strongyloidiasis.

The aim of this study was to determine whether human T-cell lymphocytotropic virus type 1 (HTLV-1) infection may affect the levels of parasite-specific immunoglobulin (Ig) G and IgE and the positivity of the skin test for strongyloidiasis. Participants included 67 patients with strongyloidiasis (40 without HTLV-1 infection and 27 coinfected with HTLV-1). We determined IgG and IgE levels by enzyme-linked immunosorbent assay, and the immediate hypersensitivity skin test was performed with the metabolic Strongyloides stercoralis antigen. Specific IgE levels and the size of skin reactions in patients without HTLV-1 were higher (P < 0.01) than those observed in patients coinfected with HTLV-1. Additionally, 89% of patients without HTLV-1 had specific IgE and 92.5% had positive skin tests; however, these values were significantly reduced (P < 0.01) in patients coinfected with HTLV-1 (44% and 59%, respectively). These data show that HTLV-1 infection decreases the sensitivity of detection of S. stercoralis-specific IgE, the size of the immediate hypersensitivity reaction, and the sensitivity of these tests in the diagnosis of strongyloidiasis.

HTLV-1 decreases Th2 type of immune response in patients with strongyloidiasis.

Eosinophils, immunoglobulin (Ig)E and cytokines have important roles in defence mechanisms against helminths. In this study, the influence of HTLV-1 infection, characterized by a Th1 type of immune response, was evaluated on the cytokine pattern and parasitic specific IgE response in patients with strongyloidiasis. Patients were divided into four groups: strongyloidiasis without HTLV-1 infection, strongyloidiasis with HTLV-1, HTLV-1 without strongyloidiasis and controls without either helminth infection or HTLV-1. The cytokine profile was determined in supernatants of mononuclear cells stimulated with Strongyloides stercoralis crude antigen and the parasite specific IgE was measured by ELISA. Patients coinfected with HTLV-1 had higher levels of interferon (IFN)-gamma and interleukin (IL)-10 (P < 0.05) and lower levels of IL-5 and IgE (P < 0.05) than patients with strongyloidiasis without HTLV-1. There was an inverse relationship between IFN-gamma and IL-5 (P = 0.01; rs = - 0.37) and between IFN-gamma and parasite specific IgE (P = 0.01; rs = - 0.39), and a direct relationship between IFN-gamma and IL-10 (P = 0.04; rs = 0.35). These data show that coinfection with HTLV-1 decreases IL-5 and IgE responses in patients with strongyloidiasis consistent with a relative switch from Th2 to Th1 response. Immunological responses such as these are important in the control of this helminthic infection.

Human T-cell lymphotropic virus type 1 infection among pregnant women in northeastern Brazil.

An evaluation of human T-cell lymphotropic virus type 1 (HTLV-1) infection among 6754 pregnant women in Salvador, Bahia, Brazil using enzyme-linked immunosorbent assay, Western blot analysis, and polymerase chain reaction assay found a rate of infection of 0.84% (57 of 6754 women). Epidemiologic and obstetric data on the HTLV-1-positive pregnant women were analyzed and compared with data on a control group of HTLV-1-negative pregnant women. The mean age of the HTLV-1-positive women was 26.2 years. All were seronegative for HIV and syphilis, and only 2 reported a past history of sexually transmitted infection and more than 10 sexual partners. Of the HTLV-1-positive women, 88.5% were breast-fed, 4% were bottle fed, and 7.5% did not know. Six women had received blood transfusions, and only 1 reported intravenous drug use. Fifty-two HTLV-1-positive women could be followed: 45 had full-term deliveries, 5 had premature deliveries, and 2 had abortions. Our results indicate that (1) the frequency of HTLV-1 infection among pregnant women is relatively high in Salvador, Bahia, Brazil; (2) maternal infection was probably acquired more frequently through breast-feeding, but the sexual route was certainly the second most important means of transmission; (3) HTLV-1-positive women had a history of eczema-like infections in childhood more frequently than the control group; (4) HTLV-1 infection did not interfere in the course of pregnancy; and (5) no associated congenital infections were observed in the HTLV-1-positive women.