Immunoproteasome beta subunit 10 is increased in chronic antibody-mediated rejection.

Chronic active antibody-mediated rejection is a form of late rejection with a poor prognosis. To identify specific markers of this, we analyzed several microarray studies in the literature and performed mRNA profiling of 65 biopsies and 165 blood samples of a large cohort of renal transplant patients with precisely characterized pathologies. Immunoproteasome beta subunit 10 was found to be specifically increased in the graft and blood samples during chronic active antibody-mediated rejection and was also significantly increased in rat cardiac allografts undergoing acute rejection as well as chronic active antibody-mediated rejection. This syndrome is characterized by chronic transplant vasculopathy associated with diffuse C4d staining and circulating donor-specific antibodies. Using this animal model, we found that administration of the proteasome inhibitor, Bortezomib, delayed acute rejection and attenuated the humoral response in both the acute phase and established state of this syndrome in a dose-dependent manner. Following treatment with this reagent, donor-specific antibodies and C4d deposition were reduced. These studies highlight the role of the proteasome in chronic rejection and identify this molecule as a marker of this syndrome.