Effect of Bortezomib Desensitization Therapy on Levels of AT1R Antibody

Abstract

Purpose Increased levels of angiotensin II type 1 receptor (AT1R) antibody have been shown to be associated with antibody mediated rejection (AMR), cell mediated rejection (CMR), and early onset of microvasculopathy at one year post heart transplant. MCS patients with the saturated levels of AT1R antibody also trend lower survival. The presence of AT1R antibody pretransplant increases risk of development of de novo donor specific antibodies posttransplant in lung transplantation. Bortezomib, a protease inhibitor, has been used for desensitization or for treatment of AMR. This study aims to determine if Bortezomib treatment can decrease the level of AT1R antibody. Methods 25 heart transplant candidates who were highly sensitized were desensitized with the Bortezomib therapy. Levels of AT1R antibody were evaluated pre-therapy, 1 month and 6 months post-therapy. Results Out of 25 patients who were treated with Bortezomib, 22 patients who were tested for AT1R antibody at all three-time points were evaluated. 8 patients had AT1R levels 17 U). Of these 14 patients, the levels of AT1R antibody decreased below 17 U in 5 patients 1 month post Bortezomib treatment. Of note, 2 patients who had the saturated levels of AT1R antibody (>40 U) remained negative ( Conclusion The Bortezomib therapy can reduce the level of AT1R antibody in some heart transplant patients. Of interest, 2 patients who were still negative for AT1R antibodies 6 month post therapy were implanted with LVAD.