Prominent HLA-G Expression in Liver Disease But Not After Liver Transplantation. Issue 12 (December 2015)

• Record Type: Journal Article
• Authors: Moroso, Viviana; van Cranenbroek, Bram; Mancham, Shanta; Sideras, Kostandinos; Boor, Patrick P. C.; Biermann, Katharina; de Vogel, Lisette; de Knegt, Robert J.; van der Eijk, Annemiek; van der Laan, Luc J. W.; de Jonge, Jeroen; Metselaar, Herold J.; Joosten, Irma; Kwekkeboom, Jaap
• Is Part Of: Transplantation. Volume 99:Issue 12(2015)
• Publication Date: 2015-12
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000000761
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Background: HLA-G is a nonclassical MHC class I molecule and its physiological expression restricted to placental extravillous trophoblasts contributes to maternal tolerance to the semiallogeneic fetus. Aberrant expression of HLA-G in human organ grafts has been proposed to contribute to graft acceptance. Methods: We studied HLA-G expression in liver tissue and serum of adult liver transplant recipients before, early, and late after transplantation in relation to liver function and operational tolerance. Results: Cirrhotic explant livers showed robust HLA-G expression on hepatocytes, whereas the majority of noncirrhotic livers and graft biopsies taken before or after liver transplantation (LTX) showed no, or weak, HLA-G expression. The HLA-G expression was induced on hepatocytes in vitro by TGF-β, but not by other relevant cytokines. Serum levels of the HLA-G isoforms 1 + 5 gradually declined after LTX. Early after LTX, serum HLA-G levels were higher in patients with acute rejection episodes than nonrejectors. Late after LTX, serum HLA-G levels did not differ between operationally tolerant patients and patients on regular immunosuppressive therapy. Conclusions: Our data do not support a graft-protective role for HLA-G after LTX, but show that end-stage liver diseases are associated with HLA-G expression on hepatocytes, which may determine a negative feedback to protect the liver against immunological damage. Abstract : The graft protective role of HLA-G in nonclassical human MHC class I molecule is studied. The authors show an association between HLA-G and end-stage liver disease but not with tolerance in immunosuppression-free liver transplant patients. Supplemental digital content is available in the text.