Human leukocyte antigen (HLA)-G displays immunotolerogenic properties toward the main effector cells involved in graft rejection through inhibition of natural killer cell- and cytotoxic T-lymphocyte-mediated cytolysis, and CD4 T-cell alloproliferation. An increase in serum and graft levels of HLA-G has been noted in transplant patients with improved allograft survival. However, the clinical relevance of soluble serum HLA-G molecules in tolerant pediatric and young adult liver transplant patients remains to be studied.
We examined the serum HLA-G levels in 42 pediatric and young adult liver transplant patients with a mean age of 15 years; 13 patients had operational tolerance (TOL), with complete immunosuppression withdrawal for 2.3 to 13.2 years.
Median HLA-G level in patients with acute rejection (AR) was similar to the level in pediatric healthy volunteers (9.9 vs. 4.2 U/mL, P=0.13). HLA-G was higher in patients with stable liver function on immunosuppression (54.6 U/mL) than in patients with AR (P=0.01) and healthy volunteers (P=0.003), but almost 6-fold lower than in TOL patients (325.4 U/mL). HLA-G did not correlate with clinical confounders or a history of posttransplant lymphoproliferative disease or Epstein-Barr virus; although levels in the TOL group were negatively correlated with time after immunosuppression withdrawal (r=-0.75, P=0.003). In rejectors, HLA-G levels trended to negatively correlate with a higher number (r=-0.58) and greater severity of AR episodes (r=-0.56) after 1 year posttransplantation.
Increased serum HLA-G levels track with operational tolerance of liver grafts and support favorable outcomes in pediatric and young adult recipients.
"HLA-G inhibits immune effectors and protects transplanted organs from rejection , . Several studies have shown a clinical correlation between expression of soluble and/or membrane-bound HLA-G and reduction of rejection risk in heart, lung, liver and kidney transplant patients or Graft versus Host disease , , , . "
[Show abstract][Hide abstract] ABSTRACT: The HLA-G molecule plays an important role in immunomodulation. In a previous study carried out on a southern French population our team showed that HLA-G haplotypes, defined by SNPs in the coding region and specific SNPs located in 5′URR and 3′UTR regulatory regions, are associated with differential soluble HLA-G expression (sHLA-G). Furthermore, the structure of these HLA-G haplotypes appears to be conserved in geographically distant populations.
The aim of our study is to confirm these expectations in a sub-Saharan African population and to explore additional factors, such as HLA-A alleles, that might influence sHLA-G expression.
DNA and plasma samples were collected from 229 Malians; HLA-G and HLA-A genotyping were respectively performed by the Snap Shot® method and by Luminex™ technology. sHLA-G dosage was performed using an ELISA kit. HLA-G and HLA-A allelic and haplotypic frequencies were estimated using an EM algorithm from the Gene[Rate] program. Associations between genetic and non genetic parameters with sHLA-G were performed using a non-parametric test with GRAPH PAD Prism 5.
Our results reveal a good conservation of the HLA-G UTR haplotype structure in populations with different origins and demographic histories. These UTR haplotypes appear to be involved in different sHLA-G expression patterns. Specifically, the UTR-2 haplotype was associated with low sHLA-G levels, displaying a dominant negative effect. Furthermore, an allelic effect of both HLA-G and HLA-A, as well as non genetic parameters, such as age and gender possibly linked to osteogenesis and sexual hormones, also seem to be involved in the modulation of sHLA-G.
These data suggest that further investigation in larger cohorts and in populations from various ethnical backgrounds is necessary not only to detect new functional polymorphism in HLA-G regulatory regions, but also to reveal the extent of biological phenomena that influence sHLA-G secretion and this might therefore have an impact on transplantation practice.
PLoS ONE 12/2013; 8(12):e82517. DOI:10.1371/journal.pone.0082517 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fibroblast-like cells with properties similar to mesenchymal stromal cells (MSCs) are present in human umbilical cord (hUC). In accordance with the international minimal criteria for defining multipotent mesenchymal stromal cells, hUC cells are designed MSCs being plastic adherent, positive to specific non hematopoietic lineage biomarkers, able to be both in vitro long term cultured and differentiated into osteoblasts, chondroblasts and adipocytes. In this review, a panoramic view of phenotypic characteristics of hUC cells derived from various UC parts are described. The high heterogeneity of extraction, culture and analysis procedures hinder the ability to precisely identify UC stromal cells. As a result, different phenotypic profiles are detectable not only among the cells obtained from the various parts of cord, but also inside the same UC regions, suggesting that UC-MSCs may represent an unique cell family whose components present various degree of stemness. However, in vitro and in vivo evidence indicates Wharton's jelly as the best source of MSCs, because its cells present a wide range of potential therapeutic applications.
[Show abstract][Hide abstract] ABSTRACT: Dendritic cells (DCs) constitute a unique set of antigen-presenting cells (APCs), equipped with the potential to initiate strong immune responses as well as to critically regulate immunity. Tolerogenic or "alternatively activated" DCs show remarkable properties in regulating immune responses both in vitro and in vivo. Furthermore, tolerogenic DCs are now beginning to be tested in clinical studies. Use of pharmacological agents to induce maturation-resistant tolerogenic DCs is a popular approach. In this review, we will discuss already recognized, as well as recently discovered, potential pharmacological agents, their mechanism of action, and the way in which they induce tolerance in DCs.
International Reviews Of Immunology 12/2010; 29(6):574-607. DOI:10.3109/08830185.2010.522280 · 4.10 Impact Factor
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