Donor-specific anti-HLA antibody monitoring and removal in solid organ transplant recipients

Abstract

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.