Antibody-mediated rejection: New approaches in prevention and management

Abstract

Estimated Time to Complete this Activity: 1.25 hours OverviewThis article reviews the pathophysiology of antibody-mediated rejection (AMR) with emphasis on the role of complement in allograft injury. It reviews the required features for a definitive diagnosis of AMR according to the latest Banff criteria, which incorporate recent findings delineating the complex spectrum of AMR and the diverse phenotypes seen. Clinical data on current and investigational treatments are summarized, and strategies to improve outcomes are presented. Lastly, a discussion of relevant predictive and surrogate endpoints provides a framework for future studies. Target AudienceThis activity has been designed to meet the educational needs of physicians, surgeons, scientists, nurses, organ procurement personnel, and pharmacists who care for patients with AMR. Educational ObjectivesAfter participating in this educational initiative, the participant should be better able to:• Explain the significance of activation of the complement system in the development of AMR Statement of SupportThis activity is jointly provided by RMEI Medical Education, LLC and Postgraduate Institute for Medicine. This activity is supported by an independent medical educational grant from Shire. For questions, please contact PIM at www.pimed.com. Joint Accreditation StatementIn support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and RMEI Medical Education, LLC. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physician Continuing Medical EducationThe Postgraduate Institute for Medicine designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credit(s) TM . Physicians should claim only the credit commensurate with the extent of their participation in the activity. Continuing Pharmacy EducationPostgraduate Institute for Medicine is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.Postgraduate Institute for Medicine designates this continuing education activity for 1.25 contact hour(s) (0.125 CEUs) of the Accreditation Council for Pharmacy Education.[Correction added on 22 March, 2018, after first online publication: The accreditation statement and CEUs were updated.] (Universal Activity Number -0809-9999-17-584-H01-P) Please note: If you participated in the activity with UAN 0809-9999-16-209-L01-P, you are not able to claim credit for this activity.For Pharmacists: Upon successfully completing the post-test with a score of 75% or better and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service. Activity Type: Application Method of Participation and Request for CreditThere are no fees for participating and receiving CME credit for this...

Proteasomal adaptations underlying carfilzomib-resistance in human bone marrow plasma cells

“…Hence, PIs now provide the foundation as a therapeutic strategy to safely and effectively treat a number of PCrelated human diseases. [8][9][10] HLA Abs, which arise from pregnancy, blood transfusion, or prior transplantation, present a significant and often impenetrable barrier to kidney transplantation, leading to increased morbidity and mortality. [5][6][7] It is now clear in kidney transplantation that Ab-mediated rejection (AMR) is the major cause of renal allograft loss, and HLA Abs also promote AMR in heart, lung, and pancreas transplantation.…”

“…[5][6][7] It is now clear in kidney transplantation that Ab-mediated rejection (AMR) is the major cause of renal allograft loss, and HLA Abs also promote AMR in heart, lung, and pancreas transplantation. [8][9][10] HLA Abs, which arise from pregnancy, blood transfusion, or prior transplantation, present a significant and often impenetrable barrier to kidney transplantation, leading to increased morbidity and mortality. 11,12 Current desensitization therapies do not impact Ab production or eliminate bone marrow plasma cells (BMPCs).…”

Technical challenges and clinical relevance of single antigen bead C1q/C3d testing and IgG subclass analysis of human leukocyte antigen antibodies

“…Because there is no standardized treatment for ABMR, clinical application of ABMR treatment greatly varies between centers while effectiveness of currently available treatment options is limited . With some novel treatments directly affecting the complement system, the complement‐fixing ability of DSA may guide the choice of treatment as well as how to monitor for treatment success.…”

Characterization of the novel HLA allele: B*14:58

“…This complex is the most polymorphic gene system in human genome encoding more than 17 000 allelic variants . The characterization and matching of HLA alleles between donor and recipient is important for the successful outcome of hematopoietic stem cell and solid organ transplantation …”

“…2 The characterization and matching of HLA alleles between donor and recipient is important for the successful outcome of hematopoietic stem cell and solid organ transplantation. [3][4][5] During the study of HLA typing of a related potential donor for stem cell transplantation, we found a sequence largely homologous to B*14:02:01 with a substitution at position 506 a C instead a G. This substitution results in a coding change from Arginine to Proline in exon 3 (codon 145b CGC ! CCC) ( Figure 1).…”