Expression of Soluble HLA-G Identifies Favorable Outcomes in Liver Transplant Recipients

Division of Nephrology, Department of Pediatrics, Stanford University, Palo Alto, CA 94304, USA.
Transplantation (Impact Factor: 3.83). 11/2010; 90(9):1000-5. DOI: 10.1097/TP.0b013e3181f546af
Source: PubMed


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.

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    • "HLA-G inhibits immune effectors and protects transplanted organs from rejection [17], [18]. 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 [19], [20], [21], [22]. "
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