Suárez-Alvarez Beatriz, López-Vázquez Antonio, Díaz-Molina Beatriz, Bernardo-Rodríguez María José, Alvarez-López Rocío, Pascual Domingo, Astudillo Aurora, Martínez-Borra Jesús, Lambert José L, González Segundo, López-Larrea Carlos
Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
Transplantation. 2006 Aug 15;82(3):354-61. doi: 10.1097/01.tp.0000228911.22944.23.
Recently the presence of a soluble form of major histocompatibility complex class I chain-related molecule A (sMICA) has been detected in the sera of patients with tumors. Shedding of sMICA by tumor cells downregulates NKG2D-mediated antitumor immunity. The aim of this investigation was to study the possible involvement of sMICA in the allograft acceptance after heart transplantation (HTX).
We monitored the levels of sMICA by specific enzyme-linked immunosorbent assay (ELISA) in a total of 146 serum samples obtained from 34 heart transplantation patients followed up during the first year post-HTX.
The persistence of sMICA expression was correlated with the clinical evolution of these patients. sMICA was detected in the serum of 21 of 34 patients (61.70%) between 15 and 20 days after implantation and was practically absent in pretransplant serum samples. Twenty of these 21 patients (95.24%) with sMICA did not experience episodes of severe rejection during this period (P = 0.0001), whereas sMICA was practically absent in patients with manifestations of severe acute rejection. The longitudinal study of these patients revealed that the presence of sMICA was consistently maintained in 75% of the patients with good graft status during the period of observation.
This has led us to believe that the presence of levels of sMICA during the first year post-HTX may contribute to allograft acceptance. Additionally, functional studies indicate that sMICA downregulates NKG2D surface expression, which may lead to a functional impairment of cell-mediated cytolysis. These data suggest a significant correlation between the presence of sMICA and a lower incidence of rejection.
最近在肿瘤患者血清中检测到了可溶性主要组织相容性复合体 I 类链相关分子 A（sMICA）。肿瘤细胞释放 sMICA 会下调自然杀伤细胞 2D（NKG2D）介导的抗肿瘤免疫。本研究旨在探讨 sMICA 在心脏移植（HTX）后同种异体移植物接受过程中可能的作用。
我们通过特异性酶联免疫吸附测定（ELISA）监测了 34 例心脏移植患者在 HTX 后第一年随访期间共 146 份血清样本中的 sMICA 水平。
sMICA 表达的持续存在与这些患者的临床病程相关。34 例患者中有 21 例（61.70%）在植入后 15 至 20 天血清中检测到 sMICA，而移植前血清样本中几乎未检测到。这 21 例 sMICA 阳性患者中有 20 例（95.24%）在此期间未发生严重排斥反应（P = 0.0001），而严重急性排斥反应患者中几乎未检测到 sMICA。对这些患者的纵向研究表明，在观察期内，75%移植状态良好的患者持续存在 sMICA。
这使我们相信，HTX 后第一年 sMICA 水平的存在可能有助于同种异体移植物的接受。此外，功能研究表明，sMICA 下调 NKG2D 表面表达，这可能导致细胞介导的细胞溶解功能受损。这些数据表明 sMICA 的存在与较低的排斥反应发生率之间存在显著相关性。
