Division of Nephrology, Department of Pediatrics, Stanford University, Palo Alto, CA 94304, USA.
Transplantation. 2010 Nov 15;90(9):1000-5. doi: 10.1097/TP.0b013e3181f546af.
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.
人类白细胞抗原（HLA）-G 通过抑制自然杀伤细胞和细胞毒性 T 淋巴细胞介导的细胞溶解以及 CD4 T 细胞同种增殖，对参与移植物排斥的主要效应细胞表现出免疫耐受特性。在移植患者中，血清和移植物中 HLA-G 水平升高与改善的同种异体移植物存活率相关。然而，可溶性血清 HLA-G 分子在具有免疫耐受的儿科和年轻成年肝移植患者中的临床相关性仍有待研究。
我们检测了 42 例年龄在 15 岁的儿科和年轻成年肝移植患者的血清 HLA-G 水平；13 例患者具有操作性耐受（TOL），完全停用免疫抑制剂 2.3 至 13.2 年。
急性排斥反应（AR）患者的中位 HLA-G 水平与儿科健康志愿者的水平相似（9.9 对 4.2 U/mL，P=0.13）。与 AR 患者（P=0.01）和健康志愿者（P=0.003）相比，接受免疫抑制治疗时肝功能稳定的患者 HLA-G 水平更高，但与 TOL 患者（325.4 U/mL）相比，HLA-G 水平低 6 倍。HLA-G 与临床混杂因素、移植后淋巴组织增生性疾病或 Epstein-Barr 病毒病史无相关性；尽管 TOL 组的 HLA-G 水平与免疫抑制剂停药后时间呈负相关（r=-0.75，P=0.003）。在排斥者中，HLA-G 水平与移植后 1 年时 AR 发作的更高数量（r=-0.58）和更大严重程度（r=-0.56）呈负相关趋势。
血清 HLA-G 水平升高与肝移植物的操作性耐受相关，并支持儿科和年轻成年受者的良好结局。
