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Immunologic Monitoring for Rejection Diagnosis during the First Three Months after Heart Transplantation

Objective: Determination of lymphocyte subset alterations during the early phase after heart transplantation. Comparison of lymphocyte activation parameters and concentrations of soluble class I MHC molecules with the established endomyocardial biopsy rejection grading results. Patients and Methods: 154 heart transplant patients with 382 endomyocardial biopsies during the first 3 months after transplantation. The following statistical data were calculated: sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic efficiency (sum of true-positive and true-negative results as a part of total results). The immunophenotyping by flow cytometry includes CD4+, CD8+, CD3/HLA-DR+, CD8/HLA-DR+ and CD4/CD25+ subsets. The activation index (activated lymphocytes defined by microscopy after staining) was also determined. Results: By shifting the cut-off of lymphocyte subsets to higher cell concentrations, the positive predictive values increased, reaching 60–100% for some parameters. However, the overall diagnostic efficiency was considerably lower: activation index 54%, CD8/HLA-DR+ 58%, CD3/HLA-R+ 57%, CD4/CD25+ 49%, and CD4/CD8-ratio 46%. The determination of soluble class I MHC molecules in plasma samples drawn during rejection episodes and in rejection-free periods in a group of 53 heart transplant patients showed no differences between the periods. Conclusions: Immunophenotyping by flow cytometry or cytology for detection of activated T lymphocytes in peripheral blood has a low overall diagnostic efficiency in rejection diagnosis. The determination of soluble class I MHC molecules seems to be of no value for the early detection of rejection.