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Serum-soluble CD4 as clinical and immunological marker in patients with dilated cardiomyopathy
G Klappacher1, M Mehrabi, K Plesch
1Department of Clinical Pharmacology, University of Vienna, Austria.
Insights
Elevated levels of cell-mediated immunity markers, particularly serum-soluble CD4, are found in dilated cardiomyopathy patients. These markers correlate with disease severity and indicate an active immune response within the heart.
Area of Science:
- Immunology
- Cardiology
- Cellular Biology
Background:
- Dilated cardiomyopathy (DCM) involves complex immune system dysregulation.
- Cell-mediated immunity markers are not well-established in DCM pathogenesis.
- Understanding immune involvement is crucial for DCM patient management.
Purpose of the Study:
- To investigate cell-mediated immunity markers in DCM patients.
- To correlate these markers with clinical severity and myocardial immune cell infiltration.
- To assess the potential of serum-soluble CD4 as a monitoring tool.
Main Methods:
- Measured serum levels of soluble CD4, soluble interleukin-2 receptor, and beta 2-microglobulin in 60 DCM patients.
- Compared marker levels with 30 healthy donors and 20 coronary artery disease controls.
- Analyzed endomyocardial biopsy samples for lymphocyte populations and infiltration patterns.
Main Results:
- DCM patients showed significantly higher levels of all tested markers compared to controls.
- Serum-soluble CD4 levels strongly correlated with clinical and hemodynamic disease stages.
- Focal myocardial lymphocytic infiltration was associated with elevated CD4/CD8 ratios and activated T-helper cells.
Conclusions:
- Cell-mediated immunity, particularly involving CD4-positive T-helper cells, is enhanced in a subset of DCM patients.
- Lymphocytic clusters in the myocardium suggest an active immune response.
- Serum-soluble CD4 is a promising biomarker for monitoring this immunopathological condition in the heart.
Abstract:
Serological markers of cell-mediated immunity, i.e., soluble CD4, soluble interleukin-2 (Il-2) receptor and beta 2-microglobulin, were determined in 60 patients with dilated cardiomyopathy. Compared with normal healthy donors (n = 30) and controls who had coronary artery disease with preserved left ventricular function (n = 20), significantly increased levels associated with the New York Heart Association functional classes have been found in the cardiomyopathy patients, irrespectively of the etiology. Out of the immunological variables tested, serum-soluble CD4 most closely reflected the clinical and hemodynamic stage, predicted the presence of lymphocytic aggregates in the myocardium and correlated with the CD4/CD8 ratios of endomyocardial lymphocytes (r = 0.6, P < 0.05). Conversely, focal mononuclear infiltration of the myocardium was associated with significantly elevated CD4/CD8 ratios (2.1 +/- 0.6 vs. 1.3 +/- 0.2, P < 0.05), higher total numbers and percentages of endomyocardial lymphocytes expressing the pan T-markers CD2 and CD3, more CD45RO/UCHL1-positive cells and more CD4-positive T-helper cells, compared with non-reactive cases the lymphocytes of which were scattered throughout the myocardium. In conclusion, in a subset of cardiomyopathy patients lymphocytic clusters in the myocardium indicated an enhanced cellular immune response predominantly mediated by CD4-positive T-helper lymphocytes with active memory function. This immunopathological condition in the heart can be monitored by serum-soluble CD4.