Sheshgiri Rohit, Rouas-Freiss Nathalie, Rao Vivek, Butany Jagdish, Ramzy Danny, Krawice-Radanne Irene, Ross Heather J, Carosella Edgardo D, Delgado Diego H
Heart Transplant Program, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
J Heart Lung Transplant. 2008 May;27(5):522-7. doi: 10.1016/j.healun.2008.02.004.
Human leukocyte antigen-G (HLA-G), a non-classical MHC I protein with restricted tissue expression, plays an essential role in immune tolerance and has been negatively associated with acute and chronic rejection after heart transplantation. We assessed myocardial HLA-G expression in adult heart transplant patients in an attempt to determine the value of this protein in identifying patients with a low risk of acute cellular rejection.
Two groups of patients were included in this study. Group A (non-rejecting) included 29 patients who had no moderate or severe rejection episodes (ISHLT Grade <2R) post-transplant. Group B (rejecting) included 38 patients with at least two moderate or severe rejection episodes (Grade >or=2R) within a 1-year period. Expression of HLA-G in three myocardial biopsies post-transplant from each patient was determined through immunohistochemical staining.
In Group A, 86% of patients had HLA-G(+) biopsies compared with 11% of patients in Group B (p < 0.001; sensitivity 86%, specificity 87%). Whereas 60% of non-rejecting HLA-G(+) patients had at least two positive biopsies, all rejecting HLA-G(+) patients had only one positive biopsy.
There is a significant negative association between myocardial HLA-G expression and acute cellular rejection after cardiac transplantation. Detection of HLA-G appears to reliably indicate a low risk of developing moderate or severe allograft rejection and may, subsequently, allow for a reduced immunosuppressive regimen.
人类白细胞抗原G(HLA-G)是一种组织表达受限的非经典MHC I类蛋白,在免疫耐受中起重要作用,并且与心脏移植后的急性和慢性排斥反应呈负相关。我们评估了成年心脏移植患者心肌中HLA-G的表达,以确定该蛋白在识别急性细胞排斥低风险患者中的价值。
本研究纳入两组患者。A组(无排斥反应组)包括29例移植后无中度或重度排斥反应发作(国际心脏和肺移植协会分级<2R)的患者。B组(有排斥反应组)包括38例在1年内至少有两次中度或重度排斥反应发作(分级≥2R)的患者。通过免疫组织化学染色测定每位患者移植后三次心肌活检中HLA-G的表达。
A组中,86%的患者活检显示HLA-G阳性,而B组中这一比例为11%(p<0.001;敏感性86%,特异性87%)。无排斥反应的HLA-G阳性患者中,60%至少有两次活检呈阳性,而所有有排斥反应的HLA-G阳性患者仅有一次活检呈阳性。
心脏移植后心肌HLA-G表达与急性细胞排斥之间存在显著的负相关。检测HLA-G似乎能可靠地表明发生中度或重度移植物排斥反应的低风险,随后可能允许减少免疫抑制方案。