Leone John P, Bowers Victor, Baliga Rajendra, Sanders Charles, LeFor William, Becker Donna, Thompson Dawn, Resto-Ruiz Sandra, Lopez-Cepero Mayra
Tampa General Medical Group at Tampa General Hospital, LifeLink Transplant Immunology Laboratory, LifeLink Foundation, Tampa, Florida, USA.
Clin Transpl. 2011:373-9.
Although the adverse allograft outcomes associated with HLA antibodies are well documented, some controversy exists regarding the importance of low-level donor specific anti-HLA antibodies (DSA). To provide further detail on this controversy, we prospectively looked at low-level DSA in negative T- and B-cell flow cytometric crossmatch (FCXM) or acceptable reactive crossmatch (ARC) patients who each underwent protocol based post-transplant antibody monitoring. HLA Class I and II antibody screening and specificity determination was conducted via a solid phase assay (SPA) and FCXM versus donor and autologous T and B cells. Post-transplant patients were immunosuppressed with quadruple maintained immunosuppressive therapy, rabbit anti-thymocyte globulin induction, and HLA antibody monitoring. Out of 31 ARC patients transplanted, 65% had a PRA > 50% and 26% showed increased DSA at 7-14 days post-transplant. Antibody mediated rejection (AMR) was treated with pharmacological and/or plasmapheresis (PP) therapy. DSA were lowered and remained at low-levels (MFI 1000- 3000) or below FCXM cutoffs. None of the 31 patients transplanted developed de-novo antibodies. Two patients lost their allografts, one to polyoma (BK) virus, and one to antibody mediated rejection (AMR). In conclusion, our experience demonstrates that patients deemed higher risk for an immunological event due to low-level DSA should be transplanted with an ARC and followed post-transplant according to an established alloantibody monitoring protocol. With close monitoring, 5-year outcomes can be expected to approach that of low-immunologic risk transplant patients.
尽管与HLA抗体相关的同种异体移植不良结果已有充分记录,但关于低水平供者特异性抗HLA抗体(DSA)的重要性仍存在一些争议。为进一步详述这一争议,我们前瞻性地观察了阴性T细胞和B细胞流式细胞术交叉配型(FCXM)或可接受的反应性交叉配型(ARC)患者中的低水平DSA,这些患者均接受了基于方案的移植后抗体监测。通过固相分析(SPA)以及与供者和自体T细胞及B细胞的FCXM进行HLA I类和II类抗体筛查及特异性测定。移植后的患者采用四联维持免疫抑制治疗、兔抗胸腺细胞球蛋白诱导治疗以及HLA抗体监测。在31例接受ARC移植的患者中,65%的患者群体反应性抗体(PRA)>50%,26%的患者在移植后7 - 14天显示DSA增加。抗体介导的排斥反应(AMR)采用药物和/或血浆置换(PP)治疗。DSA水平降低并维持在低水平(平均荧光强度1000 - 3000)或低于FCXM临界值。31例移植患者均未产生新的抗体。2例患者失去了移植物,1例因多瘤(BK)病毒感染,1例因抗体介导的排斥反应(AMR)。总之,我们的经验表明,因低水平DSA被认为发生免疫事件风险较高的患者应接受ARC移植,并根据既定的同种异体抗体监测方案在移植后进行随访。通过密切监测,预计5年结局可接近低免疫风险移植患者。