Liver transplantation
Outcome
Human Leukocyte Antigen-G, a New Parameter in the Follow-up of Liver Transplantation

https://doi.org/10.1016/j.transproceed.2005.12.108Get rights and content

Abstract

Human leukocyte antigen-G (HLA-G) displays immunotolerogenic properties toward effector cells in graft rejection through inhibition of natural killer (NK) and cytotoxic T lymphocyte (CTL)-mediated cytolysis and CD4+ T-cell alloproliferation. CD4(+)CD25(+)high regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance of pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. The aim of this study was to investigate whether there was an association between soluble and membrane-bound HLA-G levels on Treg cells and liver graft prognosis. For this purpose, we studied 37 liver transplant patients and 13 healthy blood donors. To investigate the expression of HLA-G on the surface of peripheral mononuclear (PMNL) cells, we have used monoclonal antibodies in flow cytometry to estimate CD4, CD25, CD45, and HLA-G content. HLA-G serum levels were determined by ELISA. We observed a correlation between sHLA-G serum levels and liver function tests. After a month of HLA-G decrease in serum levels, liver function tests such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin (DB), total bilirubin (TB), and alkaline phosphatase (ALP) were above normal levels, suggesting liver dysfunction or rejection. Considering these results, we concluded that the increased sHLA-G in serum and on cell surfaces may afford preliminary data on the prognosis and response to treatment in liver transplant patients.

Section snippets

Patients and methods

Thirty-seven patients receiving primary liver transplants between 2004 and 2005 were enrolled in this prospective study. Serum samples were obtained just before and at 15 and 30 days after transplantation. The control group included 13 healthy blood donor volunteers. Peripheral mononuclear (PMNL) cells were isolated by density gradient centrifugation over Ficoll/Hypaque. We added IL-10 (50 ng/mL), cyclosporine (115 μg/mL), prednisolone (115 μg/mL), or cyclosporine + prednisolone (115 μg/mL +

Results

Among the control group, the mean value of sHLA-G level in serum was 7.2 ± 8.1 μg/mL and 61.7 ± 57.2 μg/mL in plasma. The flow cytometric analysis of cell cultures showed that within the first 24 hours IL-10 increased HLA-G expression on Treg cells the most (44304.0 ± 23143.0 for 54474.0 cells/mL), whereas prednisolone produced the same expression level within 48 hours (39091.0 ± 36608 for 44914 cells/mL) (Fig 1). On the other hand, the factor which increased soluble HLA-G serum levels at the

Discussion

The induction of allograft tolerance has traditionally been a basic aim of transplantation research. Multiple data from experimental models indicate that the outcome of transplantation (rejection versus acceptance/tolerance) depends on the balance between alloreactive cytopathic lymphocytes and immunoregulatory lymphocytes. Thus, most tolerance-inducing treatments seek to reduce the number of allo-aggressive lymphocytes and, at the same time, increase the population of regulatory lymphocytes,

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Cited by (47)

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    For example, a 14-bp insertion/deletion polymorphism located in exon 8 in the 3′ untranslated region of the HLA-G gene has found to be associated with the stability and splicing pattern of the mRNA, so resulting in a lower expression of HLA-G (35), (36), (37). Furthermore, environmental factors such as donor characteristics or the type of immunosuppressive regimen used (38), (39) may also play an important role in determining HLA-G expression of solid organ recipients. Sheshgiri et al. (40) reported that everolimus upregulates HLA-G expression, an effect which was not observed with other drugs such as mycophenolate mofetil or cyclosporine.

  • Biology of the immunomodulatory molecule HLA-G in human liver diseases

    2015, Journal of Hepatology
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    Numerous studies in the field of transplantation have demonstrated an association between high levels of HLA-G expression in biopsy specimens or high blood sHLA-G levels and higher rates of graft acceptance. Indeed, this association with a better post-transplantation outcome was first demonstrated for heart transplantation [70,71], and then for the transplantation of liver [39,61,72], kidney [73,74] and lung [75] grafts and for the transplantation of hematopoietic stem cells [68]. This beneficial effect may reflect a peripheral increase in the size of the CD3+CD4low and CD3+CD8low T-cell subpopulations associated with high levels of peripheral IL-10 production [76].

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This work was supported by Baskent University project KA04/146.

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