摘要目的 探讨临床肾移植术后新生HLA-DQ抗体的产生规律及临床意义.方法 入选2012年1月至2013年12月期间在华中科技大学同济医学院附属同济医院长期随访的175例初次肾移植受者,移植前微量淋巴毒和群体反应性抗体(PRA)均为阴性,入组时间在肾移植术后6～18年(平均10年).根据入组时移植肾功能分为3组:(1)移植肾功能正常的对照组(n=94):血肌酐＜120 μmol/L;(2)慢性移植肾功能减退组(n=54):血肌酐持续＞150μmol/L达6个月以上,但尚未透析;(3)移植肾失功能组(n=27):患者恢复血液透析.所有病例在入组时收集血清,采用流式PRA或Luminex方法进行HLA抗体初筛,抗体阳性者进一步行Luminex单抗原包被的微球法检测分别针对HLA-A、B、DR、DQ位点的抗体水平.结果 (1) HLA抗体的出现与慢性移植肾功能不全密切相关.慢性移植肾功能减退组HLA抗体阳性的出现率为48％(26/54),移植肾失功能组为52％(14/27),而对照组的HLA抗体阳性率只有17％ (16/94) (P＜0.01).(2)在3组HLA抗体阳性的病例中,相比于HLA-DR、HLA-Ⅰ类抗体,HLA-DQ抗体的出现频率均最高,在对照组、慢性移植肾功能减退组、移植肾失功能组分别为14/16、24/26及14/14,此外,HLA-DQ抗体的平均荧光强度也最高.(3) HLA-DQ抗体在对照组的HLA抗体阳性病例中以单独出现为主(10/16),而在慢性移植肾功能减退组和移植肾失功能组都多数伴随有HLA-DR抗体和Ⅰ类抗体(17/26、14/14),显示单独出现的HLA-DQ抗体与慢性移植肾功能不全没有直接相关性,而DQ抗体合并DR和(或)Ⅰ类抗体同时出现与慢性移植肾功能减退和失功能有关(均P＜0.05).结论 从移植肾功能状态而言,HLA-DQ抗体往往先于其他位点的抗体出现.在临床移植肾功能尚稳定时,早期发现HLA-DQ抗体对预警免疫系统的特异性激活及后者所致的慢性移植肾功能减退或失功能具有重要意义.监测HLA-DQ抗体将为早期干预治疗和去除免疫危险因素提供第一时机.

abstractsObjective To explore the generation pattern and clinical relevance of de novo HLA-DQ antibodies in renal transplantation.Methods A total of 175 primary renal transplant recipients without pretransplant HLA antibodies were recruited from January 2012 to December 2013.The average follow-up period was 10 (6-18) years.They were divided into control group (n =94) with normal renal graft function (serum creatinine ＜ 120 μ mol/L) ; dysfunction group (n =54) with continued serum creatinine ＞ 150 μmol/L over 6 months; and graft loss group (n =27) with resumed hemodialysis.The sera were collected and screened for de novo HLA antibodies by flow PRA or Luminex mixed beads.And HLA-A,-B,-DR and-DQ specific antibodies were identified by HLA single antigen beads.Results Positive de novo HLA antibodies were detected in 48％ (26/54) of patients from dysfunction group and in 52％ (14/27) from graft loss group,but only in 17％ (16/94) from control group (P ＜ 0.01).The frequency of de novo DQ antibodies among patients with any positive HLA antibody was the highest in all three groups (14/16,24/26 and 14/14).Additionally,the average mean peak fluorescence intensity of DQ antibodies was almost the highest when compared to other antibodies.Moreover,when those with positive HLA antibodies in each group were analyzed,10/16 in control group were detected to have DQ antibodies alone.However,17/26 of patients in dysfunction group and 14/14 in graft loss group were detected to have DQ antibodies plus HLA-DR and/or-A,-B antibodies.It indicated that the combined presence of DQ-and non-DQ-antibodies was associated with chronic renal graft failure.Conclusions The presence of de novo HLA-DQ antibodies is frequent after renal transplantation.And it is associated with chronic graft failure when co-displaying with other HLA antibodies.The screening and detection of HLA-DQ antibodies after kidney transplantation may aid early warning of donor antigen-specific activation of immune system and subsequent graft dysfunction.Thus it serves as an indication for early treatment.