Everly Matthew J
One Lambda, Inc., Canoga Park, CA, USA.
Clin Transpl. 2011:319-25.
Based on our knowledge that donor specific anti-HLA antibodies (DSA) are a major cause of allograft loss, determining how to monitor patients for DSA and how to treat them is important. Current published studies indicate that patients with preformed DSA differ from those without. Approximately 15-18 percent of transplant patients will have preformed DSA, which increases risk for early antibody mediated rejection (AMR) and allograft loss. The fact that nearly all AMR episodes occur in the first 1-2 months, coupled with the finding that a reduction in preformed DSA intensity within the first few weeks post-transplant decreases the risk of AMR, makes early testing important. It has also been shown that clearance of DSA at 6 months and 1 year can result in a decreased risk of transplant glomerulopathy and therefore, these times may be prime testing points. This monitoring schedule differs slightly from that of the patients who do not have performed DSA (i.e. low risk patients). Low risk patients who develop de novo DSA are most likely to do so in the first 6 months. However, more frequent sampling in the early months does not improve predictability of acute rejections in low risk patients and therefore, it is not as essential. Rather, testing at 6 months and then annually or biannually, would be beneficial, as it would serve to identify the 5 percent of new patients who develop DSA annually. Once these patients are identified, studies have shown that preemptive treatment to a goal of antibody clearance can be used to improve graft function and survival. In addition to screening for new DSA, monitoring for clearance of DSA along with histologic reversal of rejection in patients with AMR is important. In sum, there is substantial evidence suggesting that all patients need to have some monitoring for DSA to identify new onset of DSA or clearance of DSA. Additionally, in all DSA scenarios, treatment of persistent DSA is important, as it can lead to improved allograft survival.
基于我们所知供者特异性抗HLA抗体(DSA)是同种异体移植物丢失的主要原因,确定如何监测患者的DSA以及如何对其进行治疗很重要。目前已发表的研究表明,预先存在DSA的患者与没有DSA的患者有所不同。大约15% - 18%的移植患者会预先存在DSA,这增加了早期抗体介导的排斥反应(AMR)和同种异体移植物丢失的风险。几乎所有的AMR发作都发生在头1 - 2个月,再加上移植后几周内预先存在的DSA强度降低会降低AMR风险这一发现,使得早期检测很重要。研究还表明,6个月和1年时DSA的清除可降低移植肾小球病的风险,因此,这些时间点可能是主要的检测点。这种监测方案与没有预先存在DSA的患者(即低风险患者)的监测方案略有不同。发生新发DSA的低风险患者最有可能在头6个月内出现。然而,在最初几个月更频繁地采样并不能提高低风险患者急性排斥反应的可预测性,因此并非必不可少。相反,在6个月时进行检测,然后每年或每两年检测一次会有帮助,因为这将有助于识别每年出现DSA的5%的新患者。一旦识别出这些患者,研究表明,以抗体清除为目标的抢先治疗可用于改善移植物功能和存活。除了筛查新发DSA外,监测DSA的清除以及AMR患者排斥反应的组织学逆转也很重要。总之,有大量证据表明,所有患者都需要对DSA进行一定监测,以识别DSA的新发或清除情况。此外,在所有DSA情况下,治疗持续存在的DSA很重要,因为这可提高同种异体移植物的存活率。