Heart Transplant Program, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, 585 University Avenue, Toronto, Ontario, Canada.
J Heart Lung Transplant. 2009 Nov;28(11):1193-7. doi: 10.1016/j.healun.2009.07.009. Epub 2009 Sep 26.
Human leukocyte antigen-G (HLA-G), a protein primarily expressed during pregnancy, helps maintain maternal-fetal immune tolerance. Myocardial and/or soluble HLA-G (sHLA-G) expression confers protection against rejection and vasculopathy after heart transplantation. Although the precise mechanisms remain unclear, immunosuppressive therapy has been reported to influence this expression.
We compared sHLA-G expression in heart transplant recipients receiving two different anti-proliferative agents: mycophenolate mofetil (MMF) and everolimus (RAD). Twelve-hour pharmacokinetic (PK) studies were conducted in patients after cyclosporine (CsA) administration in conjunction with RAD or MMF, during which plasma HLA-G concentrations were measured by enzyme-linked immunoassay (ELISA).
Among patients receiving RAD, 78% expressed detectable levels of plasma HLA-G (1,002 +/- 511 ng/ml) compared with 25% of patients receiving MMF (612 +/- 438 ng/ml, p = 0.03). In all sHLA-G(+) patients, expression remained constant, with no significant changes in HLA-G levels throughout the 12-hour PK study period. CsA did not appear to influence sHLA-G expression, as there was no correlation between HLA-G levels and CsA exposure (R(2) = 0.43, p = 0.08).
These preliminary findings suggest a disproportionate expression of HLA-G in patients under two distinct immunosuppression strategies after heart transplantation. Although CsA administration does not influence sHLA-G levels, RAD but not MMF is associated with sHLA-G expression. Larger prospective clinical investigations are required to confirm whether RAD is independently associated with increased HLA-G expression.
人类白细胞抗原-G（HLA-G）是一种主要在妊娠期间表达的蛋白质，有助于维持母婴免疫耐受。心肌和/或可溶性 HLA-G（sHLA-G）的表达可防止心脏移植后的排斥反应和血管病变。尽管确切的机制尚不清楚，但已报道免疫抑制疗法会影响这种表达。
我们比较了接受两种不同的抗增殖药物的心脏移植受者的 sHLA-G 表达：霉酚酸酯（MMF）和依维莫司（RAD）。在环孢素（CsA）与 RAD 或 MMF 联合给药后，对患者进行 12 小时药代动力学（PK）研究，在此期间通过酶联免疫吸附测定（ELISA）测量血浆 HLA-G 浓度。
在接受 RAD 的患者中，78％表达可检测到的血浆 HLA-G（1002±511ng/ml），而接受 MMF 的患者为 25％（612±438ng/ml，p=0.03）。在所有 sHLA-G（+）患者中，表达保持恒定，在整个 12 小时 PK 研究期间，HLA-G 水平没有明显变化。CsA 似乎不会影响 sHLA-G 的表达，因为 HLA-G 水平与 CsA 暴露之间没有相关性（R（2）=0.43，p=0.08）。
这些初步发现表明，在心脏移植后两种不同的免疫抑制策略下，HLA-G 的表达不成比例。尽管 CsA 给药不会影响 sHLA-G 水平，但 RAD 而不是 MMF 与 sHLA-G 表达相关。需要更大规模的前瞻性临床研究来证实 RAD 是否与 HLA-G 表达增加独立相关。
