Expression of soluble HLA-G identifies favorable outcomes in liver transplant recipients.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Increased serum HLA-G levels track with operational tolerance of liver grafts and support favorable outcomes in pediatric and young adult recipients.
Zarkhin
Valeriya
V
Division of Nephrology, Department of Pediatrics, Stanford University, Palo Alto, CA 94304, USA.
Talisetti
Anita
A
Li
Li
L
Wozniak
Laura J
LJ
McDiarmid
Sue V
SV
Cox
Kenneth
K
Esquivel
Carlos
C
Sarwal
Minnie M
MM
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000097:blood / Q000276:immunology; D006680:HLA Antigens / Q000097:blood*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007223:Infant; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D011237:Predictive Value of Tests; D012727:Sex Characteristics; D023001:Transplantation Tolerance / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I