Experience with Antibody-Mediated Rejection Millie Samaniego, M.D. Associate Professor of Medicine University of Wisconsin and Robert A. Montgomery, M.D., D.Phil. Chief, Division of Transplantation tor, The Johns Hopkins Comprehensive Transplant C The Johns Hopkins Hospital
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Experience with Antibody-Mediated Rejection Millie Samaniego, M.D. Associate Professor of Medicine University of Wisconsin and Robert A. Montgomery, M.D.,
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Experience withAntibody-Mediated Rejection
Millie Samaniego, M.D.Associate Professor of Medicine
University of Wisconsinand
Robert A. Montgomery, M.D., D.Phil.Chief, Division of Transplantation
Director, The Johns Hopkins Comprehensive Transplant CenterThe Johns Hopkins Hospital
•Characteristic histologic features including:1) glomerulitis/capillaritis2) margination of neutrophils in the PTC3) fibrin thrombi4) interstitial hemorrhage5) severe or necrotizing vasculitis
•Diffuse, linear C4d staining in the PTC
•Identification of DSA
Diagnostic Criteria for Acute AMR
Grade 1
Grade 3
AMR Cellular Accommodation
Patterns of Rejection in ABO Incompatible Transplants
•Anti-idiotypic networks probably important •Many putative immunomodulatory pathways identified
•Advantages:•In vitro test for predicting efficacy•Ease of administration?
•Disadvantages:•Non-responders•Different techniques required to follow DSA titers•Less rapid Ab removal, unproven for high-titer DSA•Toxicity & batch-to-batch variability•Unproven for ABOi Tx
•Rapid reduction in anti-HLA or isoagglutinin Ab•Induces donor specific unresponsiveness (HLA) or accommodation (ABOI)
•Advantages:•Predictable kinetics of plasmapheresis•No evidence of “nonresponders”•Able to easily follow DSA levels during/after therapy
•Disadvantages:•DSA may rebound between treatments or if discontinued•Treatment may be prolonged and immunosuppressive•Expensive and resource intensive
•Mechanism:•Rapid ablation of the peripheral B-cell compartment
•Advantages:•Probably reduces precursor cells responsible for clonal expansion during AMR•May produce more effective antibody reduction when combined with plasmapheresis or IVIG •Well-tolerated, little apparent toxicity •Effect on the immune system is temporary (6-months)
•Disadvantages:•Plasma cells persist in the spleen•May not, on its own, reduce DSA titers during AMR •Immunosuppressive
•Advantages:•Can be performed using minimally invasive techniques•May produce more effective antibody reduction when combined with plasmapheresis or IVIG
•Disadvantages:•Life-long risk of sepsis from encapsulated bacteria•Does not appear on its own to reduce DSA titers•Effect on immune system is permanent