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Protective human leucocyte antigen haplotype, HLA-DRB1*01-B*14, against chronic Chagas disease in Bolivia
Florencia del Puerto1, Juan Eiki Nishizawa, Mihoko Kikuchi
1Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), and Global COE Program, Nagasaki University, Nagasaki, Japan.
Insights
Human Leucocyte Antigen (HLA) gene variations influence Chagas disease progression. Specific HLA haplotypes are linked to resistance against chronic Chagas disease complications, offering new insights into disease mechanisms.
Area of Science:
- Immunogenetics
- Tropical Medicine
- Molecular Biology
Background:
- Chagas disease affects millions in Latin America, with poorly understood mechanisms of cardiac and digestive complications.
- Host genetic factors may influence the clinical course of chronic Chagas disease.
- Human Leucocyte Antigen (HLA) gene polymorphism is investigated as a potential influence on disease outcomes.
Purpose of the Study:
- To identify host genetic factors, specifically HLA polymorphisms, associated with clinical manifestations of chronic Chagas disease.
- To explore the relationship between HLA gene variations and the development of cardiac (ECG alterations) and digestive (megacolon) pathologies.
- To determine if specific HLA haplotypes are associated with resistance or susceptibility to chronic Chagas disease complications.
Main Methods:
- Analysis of 229 chronic Chagas disease patients in Bolivia using serological tests, ECG, and barium enema colon X-ray.
- Recruitment of 62 additional seropositive megacolon patients who had undergone colonectomy.
- Genotyping of HLA-A, HLA-B, MICA, MICB, DRB1, and TNF-alpha promoter region using sequence-based and LABType SSO typing with LUMINEX Technology.
Main Results:
- Significantly lower frequencies of HLA-DRB1*01 and HLA-B*14:02 alleles observed in patients with megacolon and/or ECG alterations compared to those with indeterminate symptoms.
- Identification of strong Linkage Disequilibrium (LD) between DRB1*0102, B*1402, and MICA*011 alleles.
- The HLA-DRB1*01-B*14-MICA*011 haplotype was significantly associated with resistance against chronic Chagas disease.
Conclusions:
- This study provides the first evidence of an association between a specific HLA haplotype and resistance to chronic Chagas disease.
- The findings suggest that host genetic factors, particularly HLA variations, play a crucial role in determining the clinical outcome of Chagas disease.
- Further research into HLA associations could lead to a better understanding of Chagas disease pathogenesis and potential therapeutic targets.
Background:
Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8-10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms.
Methodology:
Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology.
Principal Findings:
The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011 haplotype was associated with resistance against chronic Chagas disease.
Conclusions:
This is the first report of HLA haplotype association with resistance to chronic Chagas disease.
