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HLA class II DRB1, DQB1, DPB1 polymorphism and cardiomyopathy due to Trypanosoma cruzi chronic infection
I A Colorado1, H Acquatella, F Catalioti
1Instituto Venezolano de Investigaciones Cientificas (IVIC), Laboratorio de Fisiopatologia, Caracas and Centro de Investigaciones Jose Francisco Torrealba, San Juan de Los Morros, Venezuela.
Insights
Human leukocyte antigen (HLA) alleles are associated with Chagas disease cardiomyopathy risk. Specific HLA class II alleles, particularly DPB1*0401 combinations, significantly increase the risk of developing heart damage in Trypanosoma cruzi infected individuals.
Area of Science:
- Immunogenetics
- Cardiology
- Infectious Diseases
Background:
- Chagas disease, caused by Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America.
- Human leukocyte antigen (HLA) molecules play a role in regulating the immune response to T. cruzi infection.
- Previous research suggests an association between specific HLA antigens and the development of heart damage in Chagas disease patients.
Purpose of the Study:
- To investigate the association between HLA class II alleles and the clinical manifestations of Chagas disease cardiomyopathy.
- To identify specific HLA alleles or haplotypes that confer susceptibility or protection against heart damage in T. cruzi infected individuals.
Main Methods:
- Genotyping of HLA class II alleles using the polymerase chain reaction and sequence specific oligonucleotide (PCR-SSO) method in 111 T. cruzi antigen-seropositive individuals.
- Classification of patients into three groups: asymptomatic, with arrhythmia, and with overt congestive heart failure.
- Statistical analysis to determine the association between HLA alleles/haplotypes and clinical groups.
Main Results:
- The DRB1*01 DQB1*0501 haplotype was significantly increased in patients with cardiomyopathy (p = 0.03).
- The DPB1*0401 allele frequency was significantly higher in patients with heart disease (groups B + C) (p = 0.009), while DPB1*0101 was more frequent in asymptomatic individuals (p = 0.04).
- A combination of specific DPB1*0401 alleles conferred a 6.55-fold increased risk of developing cardiomyopathy (p = 0.041).
Conclusions:
- Specific HLA class II alleles and haplotypes are associated with the development of Chagas disease cardiomyopathy.
- The DPB1*0401 allele, particularly in certain combinations, is a significant risk factor for heart damage.
- These findings highlight the role of immunogenetics in the susceptibility to Chagas disease cardiomyopathy and may inform future diagnostic or therapeutic strategies.
Abstract:
Trypanosomiasis is an important cause of cardiomyopathy in endemic rural areas of Latin America. Previous studies have suggested participation of HLA molecules in the immune response regulation of T. cruzi infection, and association of HLA antigens with heart damage. One hundred and eleven unrelated T. cruzi antigen-seropositive individuals were tested for HLA class II alleles by the polymerase chain reaction and sequence specific oligonucleotide (PCR-SSO) method. Patients were classified in 3 groups according to clinical and electrocardiographic characteristics: asymptomatics (group A), with arrhythmia (group B), and with overt congestive heart failure (group C). Statistical analysis confirmed the significant increment of the DRB1*01 DQB1*0501 haplotype (p = 0.03) previously reported by our laboratory in patients with cardiomyopathy. The DPB1*0401 allele frequency is also significantly increased in patients with heart disease (groups B + C) (p = 0.009) while DPB1*0101 frequency is higher among the asymptomatic group (p = 0.04) compared with individuals of group C. The DPB1*0401 allele in homozygous form or in combination with allele DPB1*2301 or 3901, was found present more often in patients of groups B and C. Thus, the combination of two of these three alleles, sharing specific sequence motifs in positions 8, 9, 76, and 84-87 confers a relative risk of 6.55 to develop cardiomyopathy in seropositive patients (p = 0.041). Furthermore, 32% of the cardiomyopathics have either DRB1*01 DQB1*0501 and/or DPB1*0401/*0401, 0401/*2301, or* 0401/*3901 compared with 9% of the seropositive asymptomatics (OR = 5.0; p = 0.006).