Current challenges and opportunities in the management of antibody-mediated rejection in lung transplantation

There is increasing recognition of the importance of antibody-mediated rejection (AMR) after lung transplantation. The development of donor-specific antibodies, a key feature of AMR, occurs in approximately 30% of lung transplant recipients and is associated with poor posttransplant outcomes. This review highlights recently developed AMR diagnostic criteria in lung transplantation, potential mechanisms that mediate the development of AMR, and discusses current and emerging treatment strategies for this significant, graft-limiting complication.

A major advance is the development of consensus guidelines to precisely define AMR amongst lung transplant. Regimens for the treatment of AMR continue to evolve with varying success reported with regards to antibody clearance and improving clinical outcomes. A multimodality treatment approach is common, typically involving a combination of intravenous immune globulin, plasmapheresis, rituximab, and bortezomib or carfilzomib. Recent studies suggest several new agents including tocilizumab, belimumab, daratumumab, plerixafor, and C1 esterase inhibitor as potentially novel and effective therapies to employ in AMR treatment.

Despite advancements in the diagnosis of AMR through well defined consensus guidelines, there is limited evidence to guide treatment. Current data suggests that conventional approaches are of suboptimal efficacy, but emerging therapeutic agents with diverse biological mechanisms offer promise for improved AMR treatment.