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HLA class I and II profiles of patients presenting with Chagas' disease
N H Deghaide1, R O Dantas, E A Donadi
1Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Insights
Human Leukocyte Antigen (HLA) profiles reveal key genetic factors in Chagas disease. HLA-A30 antigen increases susceptibility, while HLA-DQB1*06 alleles offer protection against this chronic infection.
Area of Science:
- Immunogenetics
- Infectious Diseases
- Human Genetics
Background:
- Chagas' disease, caused by chronic Trypanosoma cruzi infection, presents diverse clinical manifestations.
- Understanding the genetic underpinnings, particularly Human Leukocyte Antigen (HLA) associations, is crucial for disease pathogenesis.
- Previous studies suggest a role for HLA in Chagas' disease, but comprehensive analysis across different clinical forms is needed.
Purpose of the Study:
- To investigate the association between HLA class I and II profiles and the clinical presentation of Chagas' disease.
- To identify specific HLA antigens and alleles linked to susceptibility or protection in patients with cardiac, digestive, or asymptomatic forms of the disease.
Main Methods:
- Studied 176 patients with various Chagas' disease manifestations and 448 healthy controls.
- Determined HLA class I and II specificities using serology and oligonucleotide analysis.
- Analyzed antigen and allele frequencies to calculate relative risks and etiologic/preventive fractions.
Main Results:
- HLA-A30 antigen was significantly overrepresented in patients across all clinical forms, indicating susceptibility.
- Serologic analysis suggested HLA-DQ1 conferred susceptibility and HLA-DQ7 protection, but these were not confirmed by oligonucleotide typing.
- Oligonucleotide typing revealed HLA-DQB1*06 alleles were underrepresented, conferring protection, particularly in cardiac and digestive forms.
- Asymptomatic patients showed increased HLA-DQB1*0302 specificity.
Conclusions:
- HLA-A30 antigen is a susceptibility factor for Chagas' disease, irrespective of clinical presentation.
- HLA-DQB1*06 alleles act as a protective factor against the development of Chagas' disease.
- Genetic variations in HLA influence the susceptibility and clinical outcomes of Trypanosoma cruzi infection.
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.