Lila Nermine, Amrein Catherine, Guillemain Romain, Chevalier Patrick, Latremouille Christian, Fabiani Jean-Noël, Dausset Jean, Carosella Edgardo D, Carpentier Alain
Laboratory for the Study of Cardiac Grafts and Prostheses, University of Pierre et Marie Curie, Broussais Hospital, Paris, France.
Circulation. 2002 Apr 23;105(16):1949-54. doi: 10.1161/01.cir.0000015075.89984.46.
Human leukocyte antigen (HLA)-G, a nonclassic major histocompatibility complex class I molecule expressed in the extravillous cytotrophoblast at the feto-maternal interface, is known to protect the fetus from maternal cellular immunity. In a preliminary study, we showed that HLA-G is expressed in the hearts of some patients after heart transplantation.
In the present study, a larger number of patients was investigated to confirm this finding and to look for possible correlations between HLA-G expression and the number and types of rejection. Expression of HLA-G in endomyocardial biopsy specimens was investigated by immunohistochemical analysis, and detection of the soluble HLA-G in the serum was performed by immunoprecipitation followed by Western blot analysis. HLA-G was detected in the biopsy specimens and serum of 9 of 51 patients (18%). The number of episodes of acute rejection was significantly lower in HLA-G-positive patients (1.2+/-1.1) as compared with HLA-G-negative patients (4.5+/-2.8) (P<0.001). No chronic rejection was observed in HLA-G-positive patients, whereas 15 HLA-G-negative patients had chronic rejection (P<0.032). A longitudinal study of these patients reveals that the status of HLA-G expression was maintained after 6 months both in serum and in biopsy specimens. During this period, HLA-G-positive patients did not have chronic rejection.
There is a significant correlation between rejection and HLA-G expression in the heart after transplantation. HLA-G expression and its effect in reducing the incidence and severity of rejection seem to be stable throughout the evolution.
人类白细胞抗原(HLA)-G是一种非经典的主要组织相容性复合体I类分子,在母胎界面的绒毛外细胞滋养层中表达,已知其可保护胎儿免受母体细胞免疫的影响。在一项初步研究中,我们发现心脏移植后的一些患者心脏中表达HLA-G。
在本研究中,我们调查了更多患者以证实这一发现,并寻找HLA-G表达与排斥反应的数量和类型之间可能存在的相关性。通过免疫组织化学分析研究心内膜活检标本中HLA-G的表达,并通过免疫沉淀后进行蛋白质印迹分析检测血清中可溶性HLA-G。在51例患者中的9例(18%)的活检标本和血清中检测到HLA-G。与HLA-G阴性患者(4.5±2.8)相比,HLA-G阳性患者的急性排斥反应发作次数显著更低(1.2±1.1)(P<0.001)。HLA-G阳性患者未观察到慢性排斥反应,而15例HLA-G阴性患者发生了慢性排斥反应(P<0.032)。对这些患者的纵向研究表明,血清和活检标本中HLA-G的表达状态在6个月后均得以维持。在此期间,HLA-G阳性患者未发生慢性排斥反应。
移植后心脏中的排斥反应与HLA-G表达之间存在显著相关性。HLA-G的表达及其在降低排斥反应发生率和严重程度方面的作用在整个病程中似乎是稳定的。