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Parasite Induced Genetically Driven Autoimmune Chagas Heart Disease in the Chicken Model
Published on: July 29, 2012
Expression of major histocompatibility complex antigens and adhesion molecules in hearts of patients with chronic
D D Reis1, E M Jones, S Tostes
1Departamento de Bioquimica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Insights
Chronic cardiac Chagas' disease involves heart lesions with specific immune cells. This study investigates how certain molecules on heart cells contribute to the disease's immunopathology.
Area of Science:
- Immunology
- Cardiology
- Pathology
Background:
- Chronic cardiac Chagas' disease is characterized by heart lesions dominated by cytolytic CD8+ T lymphocytes.
- Understanding the molecular interactions within these lesions is crucial for elucidating disease pathogenesis.
Purpose of the Study:
- To investigate the expression of HLA antigens and adhesion molecules in the hearts of patients with chronic chagasic cardiomyopathy.
- To determine the role of these molecules in the immunopathology of chronic chagasic cardiomyopathy.
Main Methods:
- Comparative immunohistochemical analysis of heart tissue from chagasic patients (with and without cardiac disease) and controls.
- Evaluation of HLA-ABC, HLA-DR, intercellular adhesion molecule, E-selectin, lymphocyte function antigen-1 (LFA-1), CD44, very late antigen-4, and LFA-3 expression.
Main Results:
- Enhanced HLA-ABC antigen expression on myocardial cells in patients with cardiomyopathy, suggesting a target for CD8+ T cells.
- Upregulated HLA-DR antigens on endothelial cells and E-selectin on heart vessels in patients with chronic cardiomyopathy.
- Lymphocytes within lesions express LFA-1, CD44, and very late antigen-4.
Conclusions:
- The expression of major histocompatibility complex antigens and adhesion molecules by myocardial, endothelial, and lymphoid cells contributes to the pathogenesis of chronic chagasic cardiomyopathy.
- These molecular interactions may facilitate immune cell infiltration and activity within the heart, driving cardiac damage.
Abstract:
We have previously reported that heart lesions in patients with chronic cardiac Chagas' disease are composed predominantly of granzyme A+, cytolytic CD8+ T lymphocytes. We now pursue this study in the immunopathology of chronic chagasic cardiomyopathy by investigation of the expression of HLA antigens, and adhesion molecules in the hearts of seven chagasic patients with cardiac disease, two asymptomatic chagasic patients, and seven normal controls. Comparative immunohistochemical analyses show that HLA-ABC antigen expression is enhanced on the myocardial cells of chagasic patients with chronic cardiomyopathy, suggesting a possible role for these cells as targets for the CD8+ cytolytic lymphocytes dominant in these lesions. The HLA-DR antigens are not observed on myocardial cells, but are consistently upregulated on the endothelial cells in the hearts of patients with chronic chagasic cardiomyopathy. Intercellular adhesion molecule is expressed by endothelial cells of both chagasic and nonchagasic individuals, but E-selectin was detected only on vessels of hearts from chagasic patients who had chronic cardiomyopathy. Most of the lymphocytes in these lesions express lymphocyte function antigen-1 (LFA-1), CD44, and very late antigen-4, and a few display weak expression of LFA-3. We propose that the expression of these adhesion molecules and major histocompatibility complex antigens by endothelial cells, myocardial cells, and lymphoid cells in these lesions contribute to the pathogenesis of chronic chagasic cardiomyopathy.
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