Post-transplant increase in soluble human leukocyte antigen-G associated with non-severe cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is the single most important long-term limitation to heart transplantation. This study aimed to assess the value of monitoring soluble human leukocyte antigen-G (sHLA-G) during the first year post-transplantation to predict the severity of CAV, in 21 out of 77 heart recipients assessed by intravascular ultrasound (IVUS). Serum sHLA-G concentration increased after transplant in recipients free of severe CAV, but decreased in recipients suffering from severe CAV, significant differences between these two groups were found 6 to 12 months post-transplantation. The optimal value of the change in post-transplant sHLA-G for identifying severe CAV was ≥0.062%, which maximized sensitivity (80%) and specificity (100%). Importantly, increases in post-transplant sHLA-G were inversely associated with severe CAV, but directly associated with human cytomegalovirus reactivation. In addition, recipients presenting non-severe CAV or an increased sHLA-G post-transplantation, showed higher numbers of CD8(+)CD28(-) T cells and a down-modulation of CD28 on CD4(+) lymphocytes, which typically identifies CD8(+) regulatory T cells and anergic/tolerogenic T helper cells, respectively. In conclusion, quantification of sHLA-G might offer a complementary non-invasive method for identifying recipients at risk of more severe CAV and who might benefit from earlier preventive therapies, although these results need to be confirmed in larger series.

CD28 and KIR2D receptors as sensors of the immune status in heart and liver transplantation.

Viral infections and cellular acute rejection (AR) condition immunosuppressive therapy and compromise the evolution of allografts. Immune monitoring can be useful for ascertaining rejection and for differentiating allo-reaction from activation induced by infections. This work analyzes the usefulness of monitoring the expression of CD28 and KIR2D receptors in peripheral blood T lymphocytes by flow cytometry, to ascertain the immune response in heart and liver transplant recipients. In both types of transplant, the up-regulation of CD28 in CD4(+) lymphocytes in the periods of greatest AR frequency indicates an effective allo-response, whereas the post-transplantation emergence of circulating CD8(+)CD28(-) and CD8(+)CD28(-)KIR2D(+) T cells correlates with better early clinical results. Cytomegalovirus (CMV) infection, but not hepatitis C virus (HCV) or other infections, abrogated both CD28 up-regulation and CD8(+)CD28(-)KIR2D(+) T-cell expansion. Our results show that monitoring the expression of CD28 and KIR2D receptors on T lymphocytes might be considered as sensors of the immune status of heart and liver recipients.

Divergences in KIR2D+ natural killer and KIR2D+CD8+ T-cell reconstitution following liver transplantation.

Natural killer (NK) and CD8(+) T cells may be active elements in the allograft response, but little is known about their role in liver transplantation. Some of these cells express killer immunoglobulin-like receptors (KIRs), which after binding specific ligands may transmit inhibitory/activating signals. In this study, circulating NK and CD8(+) T cells expressing CD158a/h (KIR2DL1/S1) or CD158b/j (KIR2DL2/3/S(2)) receptors were analyzed in 142 liver recipients by flow cytometry. They were underrepresented in patients before transplantation, but following transplantation, whereas the KIR2D(+) NK subsets experienced a late recuperation (day 365) mainly in C2-homozygous patients developing early acute rejection, recovery of the 2 CD8(+)KIR2D(+) T cells started earlier, showing significant differences on day 365 between patients without acute rejection and those suffering from it (p = 0.004 and p < 0.0001, respectively). These differences were also evident when the human leukocute antigen-C genotypes of the recipient were considered. In conclusion, whereas the late recovery of KIR2D(+) NK cells in C2/C2 patients appears to be linked to acute rejection, the increase in early CD8(+)KIR2D(+) T cells in overall liver recipients correlates with a most successful early graft outcome. Therefore, monitoring of KIR2D(+) cells appears to be a useful tool for liver transplant follow-up.

Expression of HLA molecules on peripheral blood lymphocytes: a useful monitoring parameter in cardiac transplantation.

During the rejection process of cardiac allografts, the expression of HLA antigens increases on various graft tissues, ie, the myocardium and the interstitial structures. However, in this type of transplant there is a paucity of knowledge about HLA expression on recipient cells, such as peripheral blood mononuclear cells. In the present study expression of HLA class I and class II antigens was monitored on peripheral blood lymphocytes prior to and during a 12-month follow-up, using flow cytometry. In our series, the frequency of acute rejection episodes was greater from the fourth to the ninth month after transplantation, coinciding with a reduction in cyclosporine blood levels. At the same time, expression of HLA class I and class II antigens significantly increased among recipients suffering from more severe acute rejection episodes compared with those showing acceptance of their grafts (P < .01). In conclusion, acute rejection episodes in cardiac transplantation were associated with up-regulation of HLA molecules on recipient peripheral blood cells. Monitoring the expression of HLA molecules on peripheral blood lymphocytes may represent an easy, noninvasive practice to individualize immunosuppressive therapy.