A Hitchhiker’s Guide to Antibody-Mediated Rejection

Antibody-mediated rejection is a major determinant of allograft survival and has evolved significantly since the era of hyperacute rejection. The Banff Classification of Allograft Pathology, first introduced in 1991, has shaped the diagnostic approach, with updates every two years refining criteria for rejection subtypes. Canonical antibody-mediated rejection is characterized by microvascular inflammation, C4d deposition, and donor-specific antibodies. However, newer classifications recognize C4d-negative and donor-specific antibody-negative rejection, highlighting alternative mechanisms of graft injury.

Sablik et al. evaluated probable antibody-mediated rejection and microvascular injury with donor-specific antibody-negative, C4d-negative rejection both associated with poorer graft outcomes. The findings underscore challenges in diagnosing antibody-mediated rejection, including false-negative C4d results, undetectable donor-specific antibodies, and non-HLA-mediated rejection mechanisms involving AT1R and MICA antibodies.

Algorithm-based classifications improve diagnostic consistency, but individualized immunosuppressive strategies remain crucial, as severity varies among patients. Future Banff iterations aim to integrate molecular diagnostics to refine rejection criteria and optimize treatment approaches

Antibody-mediated rejection is a major determinant of allograft survival and has evolved significantly since the era of hyperacute rejection. The Banff Classification of Allograft Pathology, first introduced in 1991, has shaped the diagnostic approach, with updates every two years refining criteria for rejection subtypes. Canonical antibody-mediated rejection is characterized by microvascular inflammation, C4d deposition, and donor-specific antibodies. However, newer classifications recognize C4d-negative and donor-specific antibody-negative rejection, highlighting alternative mechanisms of graft injury.

Sablik et al. evaluated probable antibody-mediated rejection and microvascular injury with donor-specific antibody-negative, C4d-negative rejection both associated with poorer graft outcomes. The findings underscore challenges in diagnosing antibody-mediated rejection, including false-negative C4d results, undetectable donor-specific antibodies, and non-HLA-mediated rejection mechanisms involving AT1R and MICA antibodies.

Algorithm-based classifications improve diagnostic consistency, but individualized immunosuppressive strategies remain crucial, as severity varies among patients. Future Banff iterations aim to integrate molecular diagnostics to refine rejection criteria and optimize treatment approaches