Abstract
Survival post–lung transplantation remains limited to ∼ 50% at 5 years, far below
survival after other solid organ transplants. Allograft rejection is a major cause
of this limited survival. At least a third of lung transplant recipients experience
acute rejection within 1 year posttransplantation. Acute rejection, though rarely
a direct cause of death, represents the principal risk factor for chronic rejection,
which is the greatest obstacle to long-term post–lung transplant survival. This article
reviews in detail the two major subtypes of acute rejection: acute cellular rejection
(ACR) and antibody-mediated rejection (AMR). ACR is diagnosed primarily by bronchoscopic
transbronchial biopsies and is defined as perivascular or peribronchiolar lymphocytic
infiltrates in the absence of infection. AMR remains poorly defined but is thought
to involve anti–donor antibodies, allograft dysfunction, and pathological evidence
of lung tissue injury or deposition of complement. Pathophysiological mechanisms,
clinical presentation, clinical significance, known risk factors, and treatment strategies
are discussed. Additionally, the limitations of current diagnostic modalities for
both ACR and AMR are explained. Emerging data on the importance of donor-specific
and non-donor-specific anti–human leukocyte antigen (anti-HLA) antibodies as well
as non-HLA antibodies are presented. Larger cohorts have improved statistical analyses
in recent years, leading to a clearer understanding of important topics related to
ACR and AMR. Further collaborative studies and multicenter trials will be key in further
advancing lung transplantation knowledge and improving outcomes in years to come.
Keywords
lung transplantation - acute rejection - humoral rejection - antibody-mediated rejection
