Correlation of CD95 and soluble CD95 expression with acute rejection status of liver transplantation

Abstract

AIM:To analyze the expression levels of soluble form of CD95, CD95 ligand (sCD95 and sCD95L, respectively) in plasma and CD95 expression on CD3 + cells in livertransplanted recipients with acute rejection (AR). METHODS:Peripheral blood mononuclear cells (PBMCs) were isolated from 30 clinically liver transplanted recipients. CD95 expression on CD3 + cells was quantitatively measured by two-color fluorescence activated cell sorter (FACS) analysis. Lymphocyte surface phenotypes of CD4, CD8, CD16 and CD56 were determined by flow cytometry. Plasma levels of sCD95 and sCD95L were detected by Enzyme Linked-Immuno-Sorbent Assay (ELISA). The results were compared with that from normal healthy volunteers (n = 15 individuals). respectively, P<0.01). In contrast, the plasma levels of sCD95L in liver-transplanted recipients were not significantly different from that in healthy individuals. RESULTS: CONCLUSION:The present results indicate that the increased CD95 expression on CD3 + cells and the increased levels of sCD95 in plasma may modify the immunological situation of the recipients after transplantation or represent the ongoing graft rejection.

HBV and HCV Infections and Acute Rejection Differentially Modulate CD95 and CD28 Expression on Peripheral Blood Lymphocytes After Liver Transplantation

“…Therefore it would be of interest to look for parameters capable of discriminating both complications, because immunosuppression used to treat rejection further increases viral load, and it also accelerates and exacerbates recurrence of hepatitis [9]. A diversity of strategies has been implemented trying to differentiate HCV recurrence from cellular AR, such as quantification of viral HCV RNA copies in liver tissue [29], intragraft immune activation gene expression profiling [30], infiltrating leukocyte or hepatocyte apoptosis rates, as well as the expression of apoptosis related molecules CD95 and CD95L [16,19,20], but none of them became a definitive test capable of distinguishing these two entities. In fact, CD95 and CD95L intragraft protein levels have been repeatedly studied, although conclusions have been drawn that any inflammatory process increased expression of these molecules.…”

“…Among others tissues, CD95 is normally expressed in the liver and in most cells of the immune system, whereas CD95L shows a more restrictive tissue distribution. Remarkably, during the cellular acute rejection of the liver graft, both CD95 and CD95L are upregulated in liver tissue [14] and at least CD95 is also positively modulated in peripheral blood mononuclear cells (PBMC) [15,16]. However, the most important finding is that CD95 is also strongly overexpressed in liver tissue from HBVinfected [17] or HCV-infected patients who have not undergone transplantation [14, 18 -20], which seems to contribute to organ damage [21].…”

Lymphocyte surface molecules as immune activation biomarkers

“…Wieland and Shipkova, Lymphocyte surface molecules 14 sCD95) in the bloodstream have been investigated to a very limited extent [76][77][78]. As suggested for sCD30, the concentration of these soluble proteins has also been considered to serve as a surrogate marker for T cell activation [79], and if true, then this would be very attractive from both analytical (commercial kits available) and pre-analytical points of view (sample stability).…”

“…can also be assessed as soluble form in the plasma (sCD95), and Wang and colleagues reported elevated sCD95 in liver transplant patients with acute rejection compared with stable nonrejection patients and healthy controls [78].…”

Significance of Alanine Aminopeptidase N (APN) in Bile in the Diagnosis of Acute Cellular Rejection After Liver Transplantation

“…Other biomarkers of ACR after renal transplantation are being investigated at present using proteomic analysis of urine [6,7]. Analogous to kidney transplantation, several studies reported the identification of serum and bile biomarkers of ACR after liver transplantation [8][9][10][11][12][13][14][15]. Our group reported previously that interleukin-6 (IL-6) in bile correlated with ACR after liver transplantation in rats and deceased liver transplantation in human [16,17].…”