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MHC class I and class II genes in Mexican patients with Chagas disease
David Cruz-Robles1, Pedro Antonio Reyes, Víctor Manuel Monteón-Padilla
1Department of Pathology, Instituto Nacional de Cardiología Ignacio Chávez, México DF, México.
Insights
Human leukocyte antigen (HLA) gene variants are linked to Chagas disease progression. Specific HLA types, like HLA-B39 and DR4, are associated with infection, while others, such as HLA-DR16, may indicate susceptibility to heart damage.
Area of Science:
- Immunogenetics
- Infectious Diseases
- Cardiology
Background:
- Chagas' disease causes significant cardiovascular issues in Latin America.
- Human leukocyte antigen (HLA) molecules modulate immune responses to Trypanosoma cruzi.
- Previous research suggests HLA antigen associations with Chagasic heart disease.
Purpose of the Study:
- To investigate the association between major histocompatibility complex (MHC) class I (HLA-A, HLA-B) and class II (HLA-DR) genes and Chagas' disease.
- To determine if specific HLA alleles are linked to the development of cardiomyopathy in infected individuals.
Main Methods:
- Genotyping of HLA-A, HLA-B, and HLA-DR loci in 66 seropositive Chagas' disease patients (with and without cardiomyopathy) and 127 healthy controls.
- Statistical analysis including frequency comparisons and odds ratio calculations to assess genetic associations.
Main Results:
- Increased frequencies of HLA-B39 and HLA-DR4 were observed in the total seropositive group compared to controls.
- HLA-A68 and HLA-B39 were more frequent in asymptomatic individuals than in those with cardiomyopathy.
- Patients with cardiomyopathy showed higher frequencies of HLA-B35 and HLA-DR16 compared to controls and/or asymptomatic individuals.
Conclusions:
- MHC alleles are potentially associated with chronic infection and cardiac complications in Chagas' disease.
- HLA-DR4 and HLA-B39 may be linked to T. cruzi infection, while HLA-DR16 might indicate susceptibility to heart damage.
- HLA-A68 could offer protection against developing cardiomyopathy in Chagas' disease.
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.
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