The percentages of rejection are indicated in bold in the upper bar of each antibody status group. follow-up and compared them to the status of anti-HLA antibodies. HLA-G plasma levels were evaluated by ELISA at seven defined pre- and post-LT time points. HLA-G plasma levels were stable over time pre-LT and were not associated with patient characteristics. The level increased until the third month post-LT, before decreasing to a level comparable to that of the pre-LT period at one year of follow-up. Such development was impartial of biological markers and immunosuppressive treatment, except with glucocorticoids. An HLA-G plasma level 50 ng/ml on day 8 after LT Nelonicline was significantly associated with a higher rejection risk. We also observed a higher percentage of rejection in the presence of donor specific anti-HLA antibodies (DSA) and an association between the increase in HLA-G plasma levels at three months and the absence of DSA. The low immunogenicity of liver allografts could be related to early elevated levels of HLA-G, which lead, in turn, to a decrease in anti-HLA antibodies, opening potential new therapeutic strategies using synthetic HLA-G proteins. Introduction The transplantation of solid organs often represents the last therapeutic option for advanced diseases. The most frequent complications are acute or chronic rejection, leading to acute or chronic allograft dysfunction and subsequent graft fibrosis. To prevent such complications, immunosuppressive therapy is required for life but is usually itself responsible for numerous complications, such as recurrent cancer, new malignancies, and opportunistic infections [1]. Among the various causes of allograft rejection, Human Leukocyte Antigen (HLA) incompatibility between donor and recipient involving both class I (-A, -B, -C) and class II (HLA-DR, -DP, -DQ) antigens is responsible for the alloresponse, including both innate and acquired immunity [2]. Concerning liver transplantation, HLA incompatibility is not taken into account in the choice of donor because of the low immunogenicity of liver transplantation (LT) relative to other organ transplants [3]. Indeed, the hepatic graft may confer protection to other co-transplanted organs [4], as also shown in combined liver-kidney transplantation [5]. Intrinsic immunoregulatory properties of the liver explain its resilience to antibody-mediated damage relative to heart or kidney allografts. One way to reduce the risk of graft rejection in organ transplantation would be to increase immunosuppressive therapies, with all their adverse side effects, or increase the tolerogenicity of the graft, hence, the interest in understanding the mechanisms involved in Nelonicline low liver immunogenicity is usually to potentially boost and transfer them. Moreover, the tolerance induced by the liver graft could be explained by the expression or secretion of HLA-G, a natural physiological molecule that induces tolerance. HLA-G is usually a nonclassical class Ib molecule first identified to be expressed at the materno-fetal interface [6] and responsible for the tolerance of the fetus to the maternal immune system. Since IL22RA1 then, many studies have shown its dual role, both beneficial in transplantation [7] and deleterious in malignancy [8]. Its immunomodulating function results from its suppressive properties on Nelonicline specific immune cells (B and T lymphocytes), innate immune cells (segmented neutrophils and natural killer cells), and antigen-presenting cells (monocytes, macrophages, and dendritic cells) [9]. Its Nelonicline immunomodulatory function differs from that of Ia or classical HLA antigens, which can be Nelonicline explained by its unique features, which are: (i) its low polymorphism, contrasting with the highly polymorphic classical HLA class I and class II antigens, (ii) the alternative splicing of its main transcript, deleting specific exons or retaining introns 4 or 2, leading to four membrane-bound and three soluble isoforms, (iii) the quit codon in exon 6, leading to a shorter protein, (iv) different regulation of its promoter from other class I genes, and (v) its restricted expression to immune-privileged tissues under physiological conditions, contrasting with the wide ubiquitous expression of class I a HLA antigens [10]. In situations of transplantation, HLA-G has been shown to be associated with a lower occurrence of acute and chronic rejection in heart, lung, and kidney transplantation [5, 11, 12]. In liver transplantation, the involvement of HLA-G in immune tolerance differs between studies [13C17] and no obvious conclusions can be drawn. Outside of transplantation, HLA-G is also associated with certain liver diseases, as it has been detected in the livers of patients infected with hepatitis C computer virus (HCV) and shown to be associated with fibrotic lesions [18]. We investigated.