Heme disposal inside heart transplants: a trigger for rejection?

Area of Science:

• Immunology
• Transplantation Biology
• Pathology

Background:

• Cardiac allograft vasculopathy (CAV) is a major cause of heart transplant failure.
• Limited effective treatments exist for CAV, often necessitating retransplantation.

Purpose of the Study:

• To investigate the role of antibodies and heme catabolism in human cardiac allograft vasculopathy.

Main Methods:

• Analysis of explanted human cardiac allografts with and without CAV.
• Identification and characterization of intragraft plasma cells and their antibody specificities.
• Clonotypic profiling of antibody-producing B cells.
• Assessment of bilirubin deposits and macrophage gene expression related to heme catabolism.

Main Results:

• A significant number of plasma cells in CAV allografts produced antibodies against bilirubin.
• Bilirubin deposits were found in CAV tissues but not in non-rejecting grafts.
• Macrophages in CAV grafts showed increased expression of heme catabolism genes.
• Bilirubin-reactive plasma cells originated from graft-infiltrating innate-like B cells.

Conclusions:

• Graft-infiltrating innate-like B cells may develop into bilirubin-reactive antibody-producing plasma cells in CAV.
• Local heme catabolism and bilirubin deposition are associated with CAV.
• Bilirubin-specific antibodies might contribute to the pathogenesis of cardiac allograft vasculopathy.