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

Abstract

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.

The Thrombogenic Role of Platelets in Valvular Atrial Fibrillation

“…Goldsmith et al, 2000c measured plasma concentrations of soluble P-selectin (a marker for platelet activation), von Willebrand factor (a marker for endothelial cell dysfunction) and fibrinogen (as an index of haemorheology and a clotting factor), in 61 patients with moderate to severe aortic valve disease in sinus rhythm, and reported that patients with aortic valve disease had higher mean plasma fibrinogen, von Willebrand factor and soluble P-selectin levels, which were not significantly different between patients with aortic stenosis or regurgitation. Also, Prohaska et al, 2008 studied the platelet function in 660 patients considered for isolated coronary artery bypass graft (CABG) surgery, and in 421 patients considered for single aortic valve replacement (AVR). Platelet function was monitored preoperatively using the platelet function analyzer device (PFA-100), and reported that due to disturbed flow and shear exposition following an initial activation, the platelets are partially degranulated, shed microparticles, and might become involved in the pathogenesis of microvascular dysfunction and thrombotic events in patients with aortic valve disease.…”