人鼠嵌合型抗IL-2R单克隆抗体诱导肾移植受者sHLA-G5的表达上调

目的 探讨可溶性人类白细胞抗原G5(sHLA-G5)的表达上调是否为肾移植受者应用抗白细胞介素2受体(IL-2R)单克隆抗体的一个新的作用机制.方法 选取2006年1月至2007年12月解放军第三○九医院全军器官移植中心施行初次肾移植受者215例,根据是否使用抗IL-2R单克隆抗体分为:抗体使用组141例,抗体未使用组74例.健康对照组69例.采集外周血用酶联免疫吸附试验(ELISA)法检测sHLA-G5表达含量,并应用蛋白印迹方法和实时定量聚合酶链反应(Realtime PCR)进行验证.结果 移植术前,抗体使用组抗体使用后sHLA-G5的表达(56±30)μg/L]高于抗体使用前(34±20)μg/L],也高于健康对照组(35±17)μg/L]和抗体未使用组(36±19)μg/L,均P＜0.05].移植术后1 d、4 d、1周、2周,抗体使用组sHLA-G5表达随时间呈现上升趋势;而抗体未使用组sHLA-G5的表达术前术后波动很小,但术后各时间点抗体使用组sHLA-G5的表达均明显高于抗体未使用组(95±35)μg/L比(54±16)μg/L;(131±24)μg/L比(75±22)μg/L;(167±44)μg/L比(62±17)μg/L;(172±35)μg/L比(45±16)μg/L,均P＜0.01].蛋白印迹法和PCR结果与ELISA法结果相一致.结论 肾移植受者早期应用抗IL-2R单克隆抗体能够诱导sHLA-G5的表达上调,这种调节利于移植物存活,降低排斥反应发生的可能性.

Abstract：

Objective To find whether the up-regulation of soluble human lecocyte antigen-G5 (sHLA-G5) levels is a new function mechanism of anti-interleukin-2 receptors (anti-IL-2R) monoclonal antibody treatment in kidney transplantation. Methods A total of 215 recipients at our centre from January 2006 to December 2007 were divided into antibody use group ( n = 141 ) and antibody non-use group ( n =74) and another healthy group (n =69). The sHLA-G5 level in peripheral blood was detected by enzymelinked immunosorbent assay (ELISA). And the expression of HLA-G5 was confirmed by Western blot and Real-time polymerase chain reaction (PCR). Results sHLA-G5 levels was (56 ± 30)μg/L in using antiIL-2 receptor monoclonal antibody before transplantation, It was higher than that before use antibody (34 ±20) μg/L], also higher than healthy group (35 ± 17) μg/L] and antibody non-use group (36 ± 19)μg/L, P ＜0. 05, respectively]. At Day 1, Day 4, Week 1, Week 2 post-transplantation, the level of sHLA-G5 of recipients with antibody use was significantly higher than that of those with antibody non-use. The values were as follows: (95 ±35) μg/L vs (54 ± 16) μg/L , (131 ±24) μg/L vs (75 ±22) μg/L ,(167±44) μg/L vs (62 ± 17) μg/L, (172 ±35) μg/L vs (45 ±16) μg/L(all P＜0.01). And the results of Western blot and RT-PCR corresponded to those of ELISA. Conclusion The preoperative use of first dose of anti-IL-2R monoclonal antibodies results in the up-regulated level of sHLA-G5. Thus it is beneficial for protecting the kidney survival and reducing the risks of acute rejection.

Up-regulation of the sHLA-G5 level by human-mouse chimeric anti-IL-2R monoclonal antibody treatment in kidney transplantation

Objective To find whether the up-regulation of soluble human lecocyte antigen-G5 (sHLA-G5) levels is a new function mechanism of anti-interleukin-2 receptors (anti-IL-2R) monoclonal antibody treatment in kidney transplantation. Methods A total of 215 recipients at our centre from January 2006 to December 2007 were divided into antibody use group ( n = 141 ) and antibody non-use group ( n =74) and another healthy group (n =69). The sHLA-G5 level in peripheral blood was detected by enzymelinked immunosorbent assay (ELISA). And the expression of HLA-G5 was confirmed by Western blot and Real-time polymerase chain reaction (PCR). Results sHLA-G5 levels was (56 ± 30)μg/L in using antiIL-2 receptor monoclonal antibody before transplantation, It was higher than that before use antibody (34 ±20) μg/L], also higher than healthy group (35 ± 17) μg/L] and antibody non-use group (36 ± 19)μg/L, P ＜0. 05, respectively]. At Day 1, Day 4, Week 1, Week 2 post-transplantation, the level of sHLA-G5 of recipients with antibody use was significantly higher than that of those with antibody non-use. The values were as follows: (95 ±35) μg/L vs (54 ± 16) μg/L , (131 ±24) μg/L vs (75 ±22) μg/L ,(167±44) μg/L vs (62 ± 17) μg/L, (172 ±35) μg/L vs (45 ±16) μg/L(all P＜0.01). And the results of Western blot and RT-PCR corresponded to those of ELISA. Conclusion The preoperative use of first dose of anti-IL-2R monoclonal antibodies results in the up-regulated level of sHLA-G5. Thus it is beneficial for protecting the kidney survival and reducing the risks of acute rejection.