Early and late acute antibody-mediated rejection differ immunologically and in response to proteasome inhibition.

BACKGROUND: The efficacy of plasma cell targeted therapies for antibody-mediated rejection (AMR) has not been defined in detail. The purpose of this study was to compare early and late acute AMR in terms of immunologic characteristics and responses with proteasome inhibitor (PI) therapy. METHODS: Renal transplant recipients with acute AMR were treated with PI-based regimens. Early acute AMR was defined as occurring within 6 months posttransplant. Immunodominant donor-specific antibody (iDSA) was defined as the DSA with the highest level. RESULTS: Results are expressed as early or late acute AMR. Thirty AMR episodes (13 early, 17 late) were treated in 12 and 16 patients. Early but not late AMR was associated with presensitization. Late AMR iDSA levels were higher, and specificities were primarily class II (DQ being most frequent). Early AMR patients demonstrated greater reduction in iDSA at 7, 14, and 30 days and at the posttreatment nadir (81.5%+21.2% vs. 51.4%+27.6%; P<0.01). Early AMR patients were more likely to demonstrate histologic resolution/improvement (87.5% vs. 53.8%; P=0.13). Both groups demonstrated significant improvement in renal function. CONCLUSIONS: Early and late AMR exhibit distinct immunologic characteristics and respond differently to PI therapy.

Bortezomib-based treatment of antibody mediated rejection in pancreas allograft recipients.

This report presents the first experience with plasma cell-targeted therapy in treating antibody mediated rejection in pancreas transplant recipients. In this experience, bortezomib provided results similar to those previously reported in kidney transplant recipients, with the exception that DSA responses were not quite as dramatic in pancreas transplant recipients. However, even in patients with antibody mediated rejection refractory to standard therapies, significant responses were obtained with the proteasome inhibitor, bortezomib. These results confirm the potential for bortezomib-based therapies in pancreas transplant recipients, and also demonstrate that rejection following pancreas transplantation may require innovative approaches to provide optimal results.