Lung autoantibodies: Ready for prime time?

Despite advances in our understanding of the immunology of lung allograft tolerance and a reduction in the rate of acute allograft rejection using contemporary immunosuppressive protocols, the rate of chronic lung allograft dysfunction (CLAD), both obstructive and restrictive, remains unacceptably high. CLAD, particularly the restrictive phenotype, is a harbinger of a foreshortened survival. The development of a consensus approach to the diagnosis of antibody-mediated rejection by the International Society for Heart and Lung Transplantation has highlighted the need for a uniform approach toward the investigation, diagnosis, implications and management of both human leukocyte antigen (HLA) and non–HLA-related antibody formation. This Perspective summarizes the current information that underpins the way forward in recognizing the potential importance of non–HLA-related antibody formation with respect to allograft injury and outcomes.