This is driven by the current understanding of the pathophysiology of AMR, rather by robust clinical trial data

This is driven by the current understanding of the pathophysiology of AMR, rather by robust clinical trial data. is a risk factor for development of chronic rejection. Further investigations are required to better define risk factors, surveillance strategies, and optimal management strategies for acute allograft rejection. for AMR, as expert experience cited cases and causes where DSA may not be detected. Further, the allowance was made for sub-clinical AMR, in which allograft dysfunction was not (yet) observed but a diagnosis of AMR might still change management. It is important to note, that unlike ACR, AMR has typically been associated with signs and symptoms or allograft dysfunction and often results in allograft failure [44, 45]. Histologic findings in AMR are nonspecific patterns of lung injury including neutrophilic capillaritis, acute lung injury with or without diffuse alveolar damage, and arteritis [46]. Deposition of complement split product C4d on the capillary endothelium has been suggested as a marker of AMR in other organ transplants. However, C4d immunofluorescence staining on lung tissue is a less reliable test, because of high background from nonspecific binding, frequent focal staining, and presence of C4d deposition in infection and reperfusion injury [8]. The diagnosis of AMR requires multidisciplinary approach including input from the clinician, the pathologist, and the allogen laboratory director, unlike ACR which is a purely histologic diagnosis. The true incidence of pulmonary AMR Exemestane is unknown. Recent studies that define AMR by the ISHLT consensus definition, report prevalence between 4.3 and 27% of lung transplant patients. The approximate time to diagnosis from transplant is between 120 and 258?days [45]. Treatment of suspected antibody-mediated rejection is, at the present time, focused on removing antibodies and depleting B cells responsible for producing antibodies. This is driven by the current understanding of the pathophysiology of AMR, rather by robust clinical trial data. In fact, there is both a paucity of randomized trials and standardization of regimens across institutions in treatment of AMR [47]. The key components of AMR treatment include plasmapheresis, intravenous immunoglobulin (IVIG), rituximab, and steroids. The limited studies that exist on the treatment of AMR use these components in combination (Fig.?2). Open in a separate window Fig. Rabbit Polyclonal to TCF2 2 Management of antibody mediated rejection Hachem and colleagues compared outcomes in 65 patients diagnosed with AMR and treated with IVIG alone versus IVIG and rituximab [48]. They observed similar rates of DSA clearance between groups, but described lower mortality among patients whose DSA cleared. It was also observed that those treated with IVIG alone had a sooner onset of CLAD and higher mortality than those treated with combination IVIG?+?rituximab, though lack of randomization limits the generalizability of this conclusion. Proteosome inhibitors (i.e., carfilzomib or bortezomib) which promote plasma cell apoptosis have been used in treatment of AMR. Ensor et al. described 14 patients with AMR who were Exemestane treated with carfilzomib in addition to fixed schedule IVIG and plasmapheresis [49]. They observed a significant reduction of DSA levels as well as an improvement in spirometry suggesting reversal of allograft dysfunction associated with AMR. Among those who did not have a DSA level reduction (non-responders), progression to CLAD and mortality was significantly higher. These studies suggest that DSA depletion is associated with favorable outcomes. Nevertheless, outcomes after AMR remain disappointing and the prognosis is poor with high rate of progression to CLAD. Additional randomized control trials with head-to-head comparison of treatments are necessary to identify the optimal management regimens. Multicenter collaboration is necessary. Conclusions Rejection remains a significant problem following lung transplantation. Acute cellular rejection, lymphocytic bronchiolitis, and AMR are all risk factors for the subsequent development of CLAD. Ongoing research is required to further identify risk factors, improve Exemestane diagnostic tools, and optimize management strategies for allograft rejection. Author contribution All authors have participated in review of the literature, data analysis, and critical revision of.