HLA class I and II profiles of patients presenting with Chagas' disease.
ABSTRACT To evaluate the HLA class I and II profiles of a large group of patients with Chagas' disease, 176 patients presenting with pure cardiomyopathy with heart failure (N = 60), cardiomyopathy without heart failure (N = 18), pure digestive tract manifestations (N = 25), cardiac plus digestive disease (N = 40), and asymptomatic patients with positive serology for chronic Trypanosoma cruzi infection (N = 33) were studied. A total of 448 normal individuals were also studied in parallel. HLA class I and II specificities were determined using serology and oligonucleotide analysis. HLA-A30 antigen was overrepresented in the total group and in the subgroups presenting with the pure cardiac (with or without heart failure) or digestive form, conferring similar relative risks and etiologic fractions on all these presentation forms. Serologic HLA class II analysis showed that HLA-DQ1 conferred susceptibility to, while HLA-DQ7 antigen conferred protection against the development of the disease in the total group of patients. Oligonucleotide typing did not confirm the HLA class II associations obtained by serology, but showed that HLA-DQB1*06 alleles were underrepresented in the total group and in the subgroups presenting with pure digestive or cardiac disease, conferring closely similar relative risks and preventive fractions. Although asymptomatic patients showed a tendency to increased HLA-A30, they presented a significant increase of HLA-DQB1*0302 specificity. In conclusion, HLA-A30 antigen conferred susceptibility to, while HLA-DQB1*06 specificity conferred protection against, the development of the disease, regardless of the form of presentation, ie, cardiac or digestive tract disease.
Article: Genes from Chagas susceptibility loci that are differentially expressed in T. cruzi-resistant mice are candidates accounting for impaired immunity.[show abstract] [hide abstract]
ABSTRACT: Variation between inbred mice of susceptibility to experimental Trypanosoma cruzi infection has frequently been described, but the immunogenetic background is poorly understood. The outcross of the susceptible parental mouse strains C57BL/6 (B6) and DBA/2 (D2), B6D2F1 (F1) mice, is highly resistant to this parasite. In the present study we show by quantitative PCR that the increase of tissue parasitism during the early phase of infection is comparable up to day 11 between susceptible B6 and resistant F1 mice. A reduction of splenic parasite burdens occurs thereafter in both strains but is comparatively retarded in susceptible mice. Splenic microarchitecture is progressively disrupted with loss of follicles and B lymphocytes in B6 mice, but not in F1 mice. By genotyping of additional backcross offspring we corroborate our earlier findings that susceptibility maps to three loci on Chromosomes 5, 13 and 17. Analysis of gene expression of spleen cells from infected B6 and F1 mice with microarrays identifies about 0.3% of transcripts that are differentially expressed. Assuming that differential susceptibility is mediated by altered gene expression, we propose that the following differentially expressed transcripts from these loci are strong candidates for the observed phenotypic variation: H2-Ealpha, H2-D1, Ng23, Msh5 and Tubb5 from Chromosome 17; and Cxcl11, Bmp2k and Spp1 from Chromosome 5. Our results indicate that innate mechanisms are not of primary relevance to resistance of F1 mice to T. cruzi infection, and that differential susceptibility to experimental infection with this protozoan pathogen is not paralleled by extensive variation of the transcriptome.PLoS ONE 02/2006; 1:e57. · 4.09 Impact Factor
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ABSTRACT: Chagas' disease contributes significantly to cardiovascular morbidity and mortality in several Latin-American countries. Previous studies have reported the effect of the human leukocyte antigen (HLA) molecules in the immune response regulation of Trypanosoma cruzi infection, and the association of HLA antigens with heart damage. We studied the major histocompatibility complex (MHC) class I (HLA-A and HLA-B), and class II (HLA-DR) genes in a sample of 66 serologically positive individuals with and without cardiomyopathy, and in 127 healthy controls. The total group of seropositive individuals revealed increased frequencies of HLA-B39 (pc=4.3x10(-5), odds ratio [OR]=3.35) and DR4 (pc=1.8x10(-5), OR=2.91) when compared to healthy controls. Increased frequencies of HLA-A68 and HLA-B39 were found in asymptomatic individuals when compared to patients with cardiomyopathy (pc=0.014, OR=4.99 and pc=0.001, OR=4.46, respectively). Also, patients with cardiomyopathy exhibited increased frequency of HLA-B35 when compared to healthy controls (pc=0.048, OR=2.56). The HLA-DR16 frequency was increased in patients with cardiomyopathy compared with asymptomatic individuals (pc=0.05, OR=No determined) and healthy controls (pc=0.02, OR=5.0). The results suggest that MHC alleles might be associated with the development of chronic infection and with heart damage in Chagas' disease. HLA-DR4 and HLA-B39 could be associated directly with the infection by T. cruzi, whereas, HLA-DR16 could be marker of susceptibility to heart damage and HLA-A68 might confer protection to develop cardiomyopathy.Human Immunology 02/2004; 65(1):60-5. · 2.84 Impact Factor