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Influence of the HLA class II polymorphism in chronic Chagas' disease
M T Fernandez-Mestre1, Z Layrisse, S Montagnani
1Centro de Medicina Experimental, IVIC, Caracas, Venezuela.
Insights
Human leukocyte antigen (HLA) class II genes may influence Chagas disease progression. Specific HLA alleles show protective effects against infection and reduced risk of heart damage in individuals with American trypanosomiasis.
Area of Science:
- Immunogenetics
- Tropical Medicine
- Cardiovascular Disease
Background:
- Chagas' disease, caused by Trypanosoma cruzi, is a significant cause of cardiovascular morbidity and mortality in the Americas.
- Human leukocyte antigen (HLA) class II molecules play a critical role in modulating immune responses.
- Polymorphisms in HLA class II genes are fundamental to controlling immune responses.
Purpose of the Study:
- To investigate the association between HLA class II alleles and the development of Chagas' disease.
- To determine if specific HLA class II alleles are linked to cardiomyopathy in Chagas' disease patients.
Main Methods:
- DNA typing was used to analyze HLA-DRB1 and DQB1 alleles in Chagas' disease patients and healthy controls.
- PCR amplification and hybridization techniques followed the 11th International Histocompatibility Workshop protocol.
- Allele frequencies were compared between patient groups (with and without cardiomyopathy) and controls.
Main Results:
- A decreased frequency of DRB1*14 and DQB1*0303 alleles was observed in Chagas' disease patients, suggesting a protective effect.
- Patients with cardiomyopathy exhibited a higher frequency of DRB1*01, DRB1*08, and DQB1*0501 alleles.
- A decreased frequency of the DRB1*1501 allele was noted in patients with heart damage.
Conclusions:
- HLA class II genes are potentially associated with susceptibility to chronic Trypanosoma cruzi infection.
- Specific HLA class II alleles may influence the development of cardiac damage in Chagas' disease.
- Further research is warranted to elucidate the role of HLA genetics in Chagas' disease pathogenesis.
Abstract:
Chagas' disease or American trypanosomiasis due to Trypanosoma cruzi has existed at least since the time of the Inca empire and contributes significantly to cardiovascular morbidity and mortality in several countries of this continent. Due to the fundamental role of human class II molecules polymorphic residues in the control of the immune response, a study was designed to define by DNA typing HLA class II alleles in a sample of 67 serologically positive individuals with and without cardiomyopathy and in 156 healthy controls of similar ethnic origin. Genomic DNA extraction, PCR amplification of the HLA-DRB1 and DQB1 second exon regions and hybridization to labelled specific probes were carried out following the 11th International Histocompatibility Workshop reference protocol. Comparison of DRB1 and DQB1 allele frequencies among the patients and control subjects showed a decreased frequency of DRB1*14 and DQB1*0303 in the patients, suggesting independent protective effects to the chronic infection in this population. Allele frequencies comparison between patients with and without cardiomyopathy showed a higher frequency of DRB1*01, DRB1*08 and DQB1*0501 and a decreased frequency of DRB1*1501 in the patients with arrhythmia and congestive heart failure. The results suggest that HLA Class II genes may be associated with the development of a chronic infection and with heart damage in Chagas' disease.