Association between the Perioperative Antioxidative Ability of Platelets and Early Post-Transplant Function of Kidney Allografts: A Pilot Study

BACKGROUND: Recent studies have demonstrated that the actions of platelets may unfavorably influence post-transplant function of organ allografts. In this study, the association between post-transplant graft function and the perioperative activity of platelet antioxidants was examined among kidney recipients divided into early (EGF), slow (SGF), and delayed graft function (DGF) groups. METHODOLOGY/PRINCIPAL FINDINGS: Activities of superoxide dismutase, catalase, glutathione transferase (GST), glutathione peroxidase, and glucose-6-phosphate dehydrogenase (G6P) were determined and levels of glutathione, oxidized glutathione, and isoprostane were measured in blood samples collected immediately before and during the first and fifth minutes of renal allograft reperfusion. Our results demonstrated a significant increase in isoprostane levels in all groups. Interestingly, in DGF patients, significantly lower levels of perioperative activity of catalase (p<0.02) and GST (p<0.02) were observed. Moreover, in our study, the activity of platelet antioxidants was associated with intensity of perioperative oxidative stress. For discriminating SGF/DGF from EGF, sensitivity, specificity, and positive and negative predictive values of platelet antioxidants were 81-91%, 50-58%, 32-37%, and 90-90.5%, respectively. CONCLUSIONS: During renal transplantation, significant changes occur in the activity of platelet antioxidants. These changes seem to be associated with post-transplant graft function and can be potentially used to differentiate between EGF and SGF/DGF. To the best of our knowledge, this is the first study to reveal the potential protective role of platelets in the human transplantation setting

Deconvoluting Post-Transplant Immunity: Cell Subset-Specific Mapping Reveals Pathways for Activation and Expansion of Memory T, Monocytes and B Cells

A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO+CD62L− effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant

Chlamydia pneumoniae infection: an additional factor for chronic allograft rejection.

Introduction Chronic rejection (CHR) of organ allografts, one of the most significant problems in modern transplantation, is not fully understood. This study sought to evaluate the influence of selected parameters on late kidney transplant function. Patients and Method The studied group consisted of eighty-six patients who received allogeneic transplants between 1988 and 1999 for leukocyte Chlamydia pneumoniae–DNA, immunoglobulin (Ig)A/IgG anti–C pneumoniae, blood lipids, ischemic damage in the donor and during organ preservation, HLA mismatch, and acute rejection episodes. Results Eighty-six patients were segregated as 26 patients (30%) with histologically proven chronic graft rejection (CHR[+]) and 59 patients (70%) without (CHR[−]). The presence of C pneumoniae–DNA in peripheral blood leukocytes was significantly more frequent in CHR(+) than CHR(−) group (46% vs 20%). Patients with leukocytes positive for C pneumoniae–DNA more frequently (50%) had CHR than patients negative for C pneumoniae–DNA (22%). CHR(+) patients showed significantly lower HDL levels (47 mg/dL vs 58 mg/dL) and higher triglyceride levels (193 mg/dL vs 148 mg/dL). To study the cumulative effect of differences between the CHR(+) and CHR(−) groups, we applied a multiple binary logistic regression analysis. An econometric model enabled us to calculate the probability of CHR for a given patient taking into account covariates chosen by means of stepwise selection: the presence of C pneumoniae–DNA in blood leukocytes, the use of continuous pulsatile perfusion in hypothermia, myocardial infarction occurrence, and triglyceride concentrations. Conclusion The presence of C pneumoniae–DNA in peripheral blood leukocytes increased the risk of CHR, which may be predicted by a multifactor analysis of chosen parameters