title: Expression of soluble HLA-G identifies favorable outcomes in liver transplant recipients.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Pediatrics, Stanford University, Palo Alto, CA 94304, USA.
authors.forename: Valeriya
authors.initials: V
authors.lastname: Zarkhin
authors.forename: Anita
authors.initials: A
authors.lastname: Talisetti
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Wozniak
authors.forename: Sue V
authors.initials: SV
authors.lastname: McDiarmid
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cox
authors.forename: Carlos
authors.initials: C
authors.lastname: Esquivel
authors.forename: Minnie M
authors.initials: MM
authors.lastname: Sarwal
mesh_terms: 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
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I