Antibody-mediated rejection of the lung: A consensus report of the International Society for Heart and Lung Transplantation

Abstract

Antibody-mediated rejection (AMR) is a recognized cause of allograft dysfunction in lung transplant recipients. Unlike AMR in other solid-organ transplant recipients, there are no standardized diagnostic criteria or an agreed-upon definition. Hence, a working group was created by the International Society for Heart and Lung Transplantation with the aim of determining criteria for pulmonary AMR and establishing a definition. Diagnostic criteria and a working consensus definition were established. Key diagnostic criteria include the presence of antibodies directed toward donor human leukocyte antigens and characteristic lung histology with or without evidence of complement 4d within the graft. Exclusion of other causes of allograft dysfunction increases confidence in the diagnosis but is not essential. Pulmonary AMR may be clinical (allograft dysfunction which can be asymptomatic) or sub-clinical (normal allograft function). This consensus definition will have clinical, therapeutic and research implications.

Chronic lung allograft dysfunction phenotypes and treatment

“…Therefore, this raises the question to which extent rCLAD overlaps with chronic antibody-mediated rejection (AMR). AMR is an acute or subacute form of graft injury wherein antibodies against donor human leukocyte antigens cause characteristic lung histology (for instance neutrophilic capillaritis) with or without evidence of endothelial C4d staining (64). The presence of HLA antibodies seems to be more associated with rCLAD compared to BOS which is in line with the hypothesis of (at least part) overlap (65).…”

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

“…Both A and B types of ACR are thought to increase the risk of development of bronchiolitis obliterans syndrome (BOS). The other form of AR, AMR, is not as well characterized but has been described as including C4d deposition in capillaries, neutrophilic capillaritis, intravascular macrophages, and acute lung injury (55,56). Preclinical models have been useful for exploring mechanisms of both ACR and AMR (summarized in Table 2).…”

Humoral immunity in phenotypes of chronic lung allograft dysfunction: A broncho-alveolar lavage fluid analysis

“…This phenomenon is, according to the International Society for Heart and Lung Transplantation (ISHLT), denominated as antibody mediated rejection (AMR). AMR is defined by the presence of circulating DSAs, clinical allograft dysfunction and histological evidence for C4d deposition accompanied with representative lung injury [7]. Besides the importance of C4d, in cardiac transplantation, correlations have also been demonstrated between C1q positive antibodies and early AMR [8].…”