**6.2. Immunoadsorption**

**6. Treatments for antibody mediated rejection**

382 Organ Donation and Transplantation - Current Status and Future Challenges

mediated injury.

**6.1. Therapeutic plasma exchange**

protocols [37, 38, 48, 49].

The success of desensitization techniques, which enabled transplantation in the setting of pre-existing DSA, represented a breakthrough in the ability to offer transplantation to highly-sensitized patients, who previously had little hope of receiving a transplant [32–34]. But early success was tempered by observations of antibody rebound, early AMR, and suboptimal long-term graft survival [35, 36]. Thus the ability to successfully perform incompatible transplants and optimize long-term outcomes is contingent upon the ability to successfully treat AMR. The first reported efforts at allograft rescue in the setting AMR employed similar techniques as were used for desensitization, namely, techniques that remove or reduce circulating antibody [37]. While removal of antibody remains the cornerstone of AMR therapy, improved understanding of the pathophysiological mechanisms of antibody production and antibody mediated injury have yielded several adjunctive treatment options which are now in various stages of application or new development. For treatment of AMR, no standard protocols exist. Published reports are generally small patient series, and reported techniques vary based on center-specific experience and expertise, as well as center-specific access to emerging therapies [38–40]. Thus, randomizedcontrolled trial data do not exist for most of these treatments. Meta-analyses are limited by patient heterogeneity, treatment regimen heterogeneity and sample size [39, 41]. Below are brief descriptions of currently existing treatment modalities, though it is important to understand that these are rarely, if ever, used as monotherapies. Most AMR treatment strategies employ a technique for antibody removal in combination with adjunctive agents to minimize antibody production and/or act at the level of the graft to minimize antibody-

Though often referred to simply as "plasmapheresis," the procedure utilized in the treatment of AMR is more accurately described as therapeutic plasma exchange (TPE). While plasmapheresis [42] technically describes plasma removal without replacement, TPE entails plasma removal with replacement of a substitute colloid component. A 1–1.5 L plasma volume exchange generally removes approximately 70% of plasma components, including anti-HLA antibodies [43]. For immunoglobulins, the durability this treatment differs dependent upon the tissue compartments in which each immunoglobulin subclass resides. IgM, which resides solely in the intravascular space, and does not significantly repopulate by re-equilibration following TPE, much unlike IgG and IgA. Re-equilibration into the intravascular space generally means that for IgG present in high concentration initially in the serum, multiple TPE treatments are required to make measurable impact on the circulating concentration [44–46]. Rates of antibody removal with TPE, as well as characteristics of rebound following treatment vary with antibody subclass and specificity, and mechanistically this remains poorly understood [47]. TPE was one of the first reported successful strategies for treatment AMR and remains a cornerstone of most current treatment Immunoadsorption (IA) is a therapy not available worldwide, but where applied has been used successfully in both desensitization and treatment of AMR. IA has the benefit of specifically removing circulating IgG, while sparing desired plasma protein components such as clotting factors [50]. IA can rapidly and efficiently deplete IgG after a small number of treatments [51–53]. A single randomized controlled trial reporting IA plus pulse steroid compared to pulse steroid alone as treatment for AMR was stopped early after an excessive number of graft failures in the control group [54].
