动态分析HLA和MICA特异性抗体对移植肾功能的影响

Dynamic analysis of the HLA and MICA specific antibody effect on renal allograft function

目的探讨肾移植前后人类自细胞抗原（HLA）和主要组织相容性一类相关链A基因（MICA）抗体特异性对移植后排斥反应和移植肾功能的影响。方法采用免疫荧光液相芯片技术检测27例肾移植（尸供22例，亲属活体供肾5例）受者手术前后抗HLA抗体和MICA抗体的特异性和阳性值变化，并结合供受者的基因分型，区分供体特异性抗体和非供体特异性抗体。取同期的临床资料和SCr水平进行分析。结果27例移植患者中带肾存活26例，移植肾失功1例。移植后1、3、6、12个月时动态随访24例，失访2例。27例患者移植前预存抗体7例（25．9％），其中HLA抗体阳性2例、MICA抗体阳性3例、HLA和MICA抗体均阳性2例。肾移植前HLA和MICA抗体均阴性者中移植后3～6个月产生新生抗体3例。1例新生HLA-Ⅱ类特异性抗体者，移植半年后出现慢性排斥反应，经治疗术后1年SCr〉200μmol／L。3例。肾移植前MICA抗体阳性者，术后MICA抗体的特异性均无改变，但抗体的阳性分值呈现2～8分的变化，1年后均升高到移植前（4～8分）水平。移植前预存低阳性率HLA-Ⅱ类特异性抗体者1例，移植后2周有发热等排斥反应，巨细胞病毒检测阳性，移植后1个月时SCr为171μmol／L，3个月升高到236μmol／L。24例分为抗体阴性组（14例）和抗体阳性组（10例）。移植后1个月和1年时SCr水平2组间比较差异有统计学意义（P=0．03，0．05）。结论移植后3～6个月是新生抗体变化的重要随访时间，可根据HLA和MICA抗体的特异性和阳性分值变化，尽早采取有效方法预防排斥反应和减少移植肾功能减退的发生和发展。

Objective To study the influence of human leucocyte antigen（HLA） and major histoeompatibility complex class Ⅰ chain-related gene A（MICA） specific antibodies on renal allograft function and graft rejective reaction by monitoring their changes from preoperative to postoperative periods. Methods Twenty seven patients with renal allografts were tested with the specificity of anti-HLA antibodies （anti-HLA class Ⅰ and anti-HLA class Ⅱ ） and anti MICA antibodies and their positive value changes by flow PRATM beads. The HLA genotype was integrated to distinguish donor specific antihody（DSA） and non donor specific antibody（NDSA）. Their serum ereatinine levels and clinical data were analyzed simultaneously. Results Of the 27 patients, 22 cases accepted renal transplantation from dead bodies and 5 cases accepted from live donors. Except 1 failed patient, the other 26 patients had good functional renal allografts. Twenty-four survival patients were followed up on month 1, 3, 6 and 12 after transplantation. Seven out of 27 patients had pre-exist antibody beforetransplantation. Among them, 2 patients had anti-HLA antibody; 3 patients had anti MICA antibody; 2 patients had both anti HLA and anti MICA antibody. Three patients with no anti HLA and anti- MICA antibodies before transplantation created antibodies after transplantation from 3 to 6 months. One patient created NDSA after transplantation and appeared chronic rejection. There were 3 patients who had anti-MICA antibodies before transplantation. The expression levels of antibodies had changed from high to low, but the specific anti-MICA antibody had not changed during the follow up on month 1, 3, 6 and 12 after transplantation. The patient with pre transplantation low level of anti-HLA class Ⅱ antibody appeared acute rejection with fever and his CMV was positive as well. The patient＇s SCr levels changed from 171 μmol/L to 236 μmol/L. after 1 to 3 months post-transplantation. Twenty four patients were divided into positive and negative groups according to the specific antibody. There was significant difference of SCr levels between the 2 groups 1 month and 1 year after transplantation（P= 0.03, 0.05）. Conclusions It is important to detect the specificity and positive value of anti-HLA antibodies and anti-MICA antibody regularly during the post transplantation follow up. This will make an effective therapy for decreasing the occurrence and development of acute or chronic rejection and hypofunction on renal allograft.