Soluble HLA-G Expression and Renal Graft Acceptance

Qiu, Jianxin; Terasaki, Paul I.; Miller, John S.; Mizutani, Kazuo; Cai, Junchao; Carosella, Edgardo D.

doi:10.1111/j.1600-6143.2006.01417.x

Cited by 107 publications

(76 citation statements)

References 32 publications

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“…Recently, Terasaki and colleagues (29) reported the presence of HLA-G in the plasma of North American cohort of renal-transplanted patients receiving conventional immunosuppressive regimen and who had a better graft outcome and lower frequency of donor-specific Abs. This suggested that HLA-G production is not limited to combined liver-kidney transplantation and led us to investigate whether it can be present in patients treated with new immunosuppressive drugs such as CTLA4-Ig (3, 6).…”

Section: Discussionmentioning

confidence: 99%

“…In human allotransplantation, HLA-G has been detected in vivo in plasma and grafts from kidney (29), liver (30), and combined liver-kidney (31) transplant patients who experienced better graft acceptance. Increased HLA-G plasma levels correlated with a reduced incidence of acute and chronic rejection after heart, liver, and combined liver-kidney transplantation.…”

mentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Studies carried out in transplant recipients have made the following observations: i) in renal allograft recipients, the presence of serum sHLA-G is positively correlated with functioning transplants [52], ii) heart transplanted patients displaying a significant increase in serum sHLA-G in the first month after transplantation have a lower incidence of severe rejection episodes than patients with low levels of the molecule [53], and iii) in liver transplanted patients, high serum levels of sHLA-G showed a positive correlation with normal liver function tests, whereas a fall in sHLA-G levels was rapidly followed by deterioration of liver functional parameters [25,54].…”

Section: Ii) Transplantationmentioning

confidence: 99%

Soluble HLA-G: Are they clinically relevant?

Pistoia¹,

Morandi²,

Wang³

et al. 2007

Seminars in Cancer Biology

160

182

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HLA-G is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. Its main function in physiological conditions is to abrogate maternal NK cell activity against foetal tissue and to establish immune tolerance at maternal-foetal interface. HLA-G is expressed not only as a membrane bound molecule on the surface of cells, but also as a soluble moiety in body fluids. The major isoforms of HLA-G present in serum are soluble HLA-G1 and HLA-G5 which are generated by shedding or proteolytic cleavage of the membrane bound isoform and by secretion of a soluble isoform, respectively.Here we review the data about soluble HLA-G (sHLA-G) serum levels in different pathological conditions, including immune-mediated disorders, transplantation, and malignancies. In particular, we focus on sHLA-G expression and function in human neuroblastoma, a pediatric tumor, with special emphasis on a novel potential immuno escape mechanism utilized by NB to instruct monocytes to produce and release sHLA-G. Finally, the potential clinical relevance of sHLA-G serum levels is discussed.

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“…Recently, HLA-G attracted attention in the field of transplantation. With limited polymorphism and immunotolerance, upregulated HLA-G expression in grafts and plasma has been reported to correlate with allograft acceptance (21,22).…”

Section: Discussionmentioning

confidence: 99%