OUTCOMES Human Leukocyte Antigen-G, a New Parameter in the Follow-up of Liver Transplantation B. Bas ¸ türk, F. Karakayalı, R. Emirog ˘ lu, O. Sözer, A. Haberal, D. Bal, and M. Haberal 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 transplan- tation 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. H UMAN LEUKOCYTE ANTIGEN-G (HLA-G) is a nonclassical major histocompatibility complex (MHC) class I molecule of low polymorphism and restricted tis- sue distribution which displays tolerogenic functions. Four membrane-bound (HLA-G1 through G4) and three soluble HLA-G isoforms (HLA-G5 through G7) 1,2 interact with inhibitory receptors such as Ig-like transcript-2 (ILT-2) and Ig-like transcript-4 (ILT-4). These receptors are mainly expressed on natural killer (NK) cells which play a minor role in allogeneic responses to organ transplantations. ILT-2 and ILT-4 are also present on CD4 cells, CD8 cells, and antigen presenting cells. CD4 cells and CD8 cells are the most important cells in the allogeneic response to organ transplantation. 3,4 HLA-G interacts with CD4 T cells and dendritic cells that are involved in the initiation of the alloimmune response. HLA-G suppresses CD4 + T-cell proliferation in response to allogeneic stimulation 5,6 and promotes Th2 responses. 7 In human allotransplantation, From the Immunology Unit (B.B.) and Department of General Surgery (F.K., R.E., M.H.), Baskent University, Faculty of Medi- cine, Ankara, Turkey; the Hematology Research Laboratory, Baskent University, Adana Hospital, Adana, Turkey (O.S.); and the Biochemistry Laboratory, Baskent University, Ankara Hospi- tal, Ankara, Turkey (A.H., D.B.). This work was supported by Baskent University project KA04/ 146. Address reprint requests to Bilkay Bas ¸ türk, MD, PhD, Depart- ment of Internal Medicine/Immunology Unit, Baskent University, Faculty of Medicine, 12. Sokak No 7/5 Bahcelievler, 06490 Ankara, Turkey. E-mail: bilkayy@superonline.com © 2006 by Elsevier Inc. All rights reserved. 0041-1345/06/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2005.12.108 Transplantation Proceedings, 38, 571–574 (2006) 571