Human leukocyte antigen-G expression after kidney transplantation is associated with a reduced incidence of rejection

Crispim, Juliane de Almeida; Duarte, Roberta; Soares, Christiane Pienna; Costa, R. S.; Silva, João; Mendes-Junior, Celso Teixeira; Wastowski, Isabela Jubé; Faggioni, L. P. C.; Saber, Luciana Tanajura Santamaria; Donadi, Eduardo Antônio

doi:10.1016/j.trim.2007.10.010

Cited by 73 publications

(54 citation statements)

References 27 publications

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“…In transplantation, the expression of HLA-G is associated with allograft acceptance. Patients with HLA-G expression in their plasma experience significantly reduced acute rejection episodes and the absence of chronic rejection compared with HLA-G-negative patients (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of HNF-1α Mutations Associated with Familial Young-Onset Diabetes on Target Gene Regulation

Galán

García-Herrero

Azriel

et al. 2010

Mol Med

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Section: Introductionmentioning

confidence: 99%

Differential Effects of HNF-1α Mutations Associated with Familial Young-Onset Diabetes on Target Gene Regulation

Galán

García-Herrero

Azriel

et al. 2010

Mol Med

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“…Increased HLA-G plasma levels correlated with a reduced incidence of acute and chronic rejection after heart, liver, and combined liver-kidney transplantation. In transplant patients, HLA-G was detected in situ in cells that are the primary targets of the immune system in graft rejection, (i.e., endomyocardial cells, biliary epithelial cells, and tubular epithelial cells (31)(32)(33)) and exerted a local immunoregulatory properties promoting a better graft acceptance. In this study, we investigated whether the novel immunosuppressive therapeutic approach based on CTLA4-Ig regimen promotes HLA-G expression and whether HLA-G contributes to CTLA4-Ig-mediated immunosuppression.…”

mentioning

confidence: 99%

Dendritic Cells Secrete the Immunosuppressive HLA-G Molecule upon CTLA4-Ig Treatment: Implication in Human Renal Transplant Acceptance

Bahri

Naji

Menier

et al. 2009

The Journal of Immunology

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CTLA4-Ig (Belatacept) is a new recombinant molecule that interferes with the signal of T lymphocyte activation and prevents acute rejection after renal transplantation. HLA-G acts as a naturally tolerogenic molecule in humans. In this study, we analyzed whether HLA-G contributes to CTLA4-Ig-mediated graft acceptance. Our results demonstrate that patients treated with CTLA4-Ig displayed significantly higher soluble HLA-G (sHLA-G) plasma concentrations (72 ± 14 ng/ml) than patients treated with calcineurin inhibitors (5 ± 1 ng/ml) or healthy donors (5 ± 5 ng/ml). Notably, sHLA-G purified from plasma of CTLA4-Ig-treated patients was biologically active as it inhibited allogeneic T cell proliferation in vitro. Dendritic cells (DC) were identified as one of the cellular sources of sHLA-G in CTLA4-Ig-treated patients. Supporting this observation, we showed that DC generated in vitro in presence of CTLA4-Ig released sHLA-G in response to allostimulation. These CTLA4-Ig-treated DC acted as tolerogenic APC through sHLA-G secretion as they suppressed T cell alloproliferation, which could be restored by using a neutralizing anti-HLA-G Ab. These data define a novel pathway by which CTLA4-Ig immunomodulates allogenic response through posttranscriptional regulation of HLA-G expression in DC. CTLA4-Ig-mediated HLA-G release appears as a critical factor in T cell alloresponse inhibition, thereby contributing to the immunosuppressive effect and graft acceptance.

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“…The effects of HLA-G also may be enhanced by up-regulation of inhibitory receptors in CD4+ cells via interactions with these inhibitory receptors and activation of a positive feedback loop. 12 In addition to protecting against NK cells and T cells, HLA-G has been shown to inhibit antigen presenting cell (APC) function, by a mechanism that mediates evasion of the adaptive immune response. Interactions between recombinant HLA-G complexes and the ILT4 receptor on human dendritic cells, in vitro, results in impaired dendritic cell maturation, characterized by reduced cell surface expression of MHC-II and costimulatory molecules, known to be induced by the maturation stimulus.…”

Section: Introductionmentioning

confidence: 99%

“…10,14 According to Crispim and his colleagues treatment with tacrolimus (Prograf) but not with cyclosporine is associated with increased expression of HLA-G and absence of rejection. 12 This indicates that increased HLA-G expression after kidney transplant may be related to the immunosuppressive treatment to prevent rejection. Glucocorticoids enhance the level of HLA-G transcripts in cultured trophoblast cells, which were one of the first cells reported to produce HLA-G.…”

Section: Introductionmentioning

confidence: 99%

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Untitled

2015

Exp Clin Transplant

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Objectives: Studying immune tolerance induced by HLA-G in kidney allograft acceptance may help understanding of its mechanisms, hoping in the future to boaster it and decrease the immunosuppressive drugs given that are well known to have serious adverse effects. Materials and Methods: The current study sought to evaluate soluble HLA-G in 3 groups: kidney transplanted patients with no rejection episodes, transplanted patients with biopsy-proven renal rejection, and healthy age-matched non transplanted individuals.Three groups were studied: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); healthy, age-matched, nontransplanted individuals as controls (n = 42). Soluble HLA-G level was measured in the serum by a quantitative sandwich enzyme linked immunosorbent assay. Results: sHLAG level was significantly higher in the transplanted patients compared with the control. Prograf and not cyclosporine or Rapamune had positive effects on sHLAG levels. Patients with chronic rejection had a significant lower level of sHLAG compared with a graft stable group. No effect of donor type, infection or duration posttransplant, on sHLAG levels was found. Conclusions:The results of the current study are consistent with previous studies addressing the role of sHLAG in inducing immunotolerance postkidney transplant. The findings from the current study on the chronic rejection group, supports the on-going research of having a treatment with HLA-G/or derivate, which may constitute in the future a novel efficient anti-graft rejection therapy.

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Human leukocyte antigen-G expression after kidney transplantation is associated with a reduced incidence of rejection

Cited by 73 publications

References 27 publications

Differential Effects of HNF-1α Mutations Associated with Familial Young-Onset Diabetes on Target Gene Regulation

Differential Effects of HNF-1α Mutations Associated with Familial Young-Onset Diabetes on Target Gene Regulation

Dendritic Cells Secrete the Immunosuppressive HLA-G Molecule upon CTLA4-Ig Treatment: Implication in Human Renal Transplant Acceptance

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