Implication of HLA-G molecule in heart-graft acceptance

Lila, Nermine; Carpentier, Alain; Amrein, C.; Khalil-Daher, Iman; Dausset, J; Carosella, Edgardo D.

doi:10.1016/s0140-6736(00)02386-2

Cited by 202 publications

(160 citation statements)

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“…In a preliminary study, we showed that HLA-G was expressed in the hearts of some patients after heart transplantation, but the number of patients was limited. 19 The aim of the present retrospective study was to confirm this finding in a larger number of patients followed for a longer period of time and to assess whether there was a correlation between the rejection phenomena and HLA-G expression.…”

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confidence: 62%

Human Leukocyte Antigen-G Expression After Heart Transplantation Is Associated With a Reduced Incidence of Rejection

et al. 2002

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Background — Human leukocyte antigen (HLA)-G, a nonclassic major histocompatibility complex class I molecule expressed in the extravillous cytotrophoblast at the feto-maternal interface, is known to protect the fetus from maternal cellular immunity. In a preliminary study, we showed that HLA-G is expressed in the hearts of some patients after heart transplantation. Methods and Results — In the present study, a larger number of patients was investigated to confirm this finding and to look for possible correlations between HLA-G expression and the number and types of rejection. Expression of HLA-G in endomyocardial biopsy specimens was investigated by immunohistochemical analysis, and detection of the soluble HLA-G in the serum was performed by immunoprecipitation followed by Western blot analysis. HLA-G was detected in the biopsy specimens and serum of 9 of 51 patients (18%). The number of episodes of acute rejection was significantly lower in HLA-G-positive patients (1.2±1.1) as compared with HLA-G-negative patients (4.5±2.8) ( P <0.001). No chronic rejection was observed in HLA-G-positive patients, whereas 15 HLA-G-negative patients had chronic rejection ( P <0.032). A longitudinal study of these patients reveals that the status of HLA-G expression was maintained after 6 months both in serum and in biopsy specimens. During this period, HLA-G-positive patients did not have chronic rejection. Conclusions — There is a significant correlation between rejection and HLA-G expression in the heart after transplantation. HLA-G expression and its effect in reducing the incidence and severity of rejection seem to be stable throughout the evolution.

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Human Leukocyte Antigen-G Expression After Heart Transplantation Is Associated With a Reduced Incidence of Rejection

et al. 2002

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“…The constitutive expression of HLA-G proteins in extravillous cytotrophoblasts (13), and in a few other tissues (14)(15)(16), correlates with high transcriptional activity, whereas levels of HLA-G gene transcripts are generally low or absent in other tissues (17). HLA-G is also activated in virusinfected cells (18,19), in tumoral (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) and inflammatory (30)(31)(32) pathologies, and during allogenic processes (33)(34)(35).…”

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confidence: 99%

HLA-G gene repression is reversed by demethylation

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Rousseau

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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The HLA-G molecule plays an important role in immune tolerance, protecting the fetus from maternal immune attack, and probably contributes to graft tolerance and tumor escape from the host immune system. HLA-G expression is tightly regulated and involves mechanisms acting in part at the transcriptional level. Nevertheless, almost all regulatory sequences that govern constitutive and inducible HLA class I gene transcription are disrupted in the HLA-G gene promoter, suggesting an unusual regulatory process. In further investigating the molecular mechanisms of HLA-G gene activation, we evaluated the influence of epigenetic mechanisms on seven HLA-G-negative cell lines that exhibit various phenotypes. Exposure of cells to histone deacetylase inhibitors, or to the demethylating agent 5-aza-2 -deoxycytidine, revealed that HLA-G gene transcription is inhibited by DNA methylation. Reversal of methylation-mediated repression may directly induce HLA-G cellsurface expression, supporting the idea that HLA-G might be activated by such a mechanism during malignancy, inflammation, and allogenic reactions.

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“…Other immunomodulatory roles, such as its capacity to elicit a T-cell receptor-restricted response in transgenic mice (10), to trigger apoptosis of activated T and NK cells bearing the CD8 molecule (11), to impair NK cell migration (12), and to modulate cytokine (13,14) or the function of B or myelomonocytic cells bearing killing inhibitory receptors, have also been evoked. Tissue-specific patterns of HLA-G expression and their frequent alteration in pathological situations such as pregnancy disorders (15), viral infections (16 -19), tumors (20 -24), or transplantation (25) may modulate the mounting of an efficient immune response and thus provide an additional mechanism to escape immune surveillance.…”

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confidence: 99%