Chronic Antibody-Mediated Rejection and Plasma Cell ER Stress: Opportunities and Challenges with Calcineurin Inhibitors
Journal
International Journal of Molecular Sciences
Journal Volume
26
Journal Issue
6
Start Page
2711
ISSN
1422-0067
Date Issued
2025-03-18
Author(s)
Abstract
Chronic alloantibody-mediated rejection (cAMR) remains a major challenge in transplant immunology, with no FDA-approved targeted therapies currently available. Despite advancements in cellular immunosuppression, effective strategies to mitigate alloantibody-mediated rejection are still lacking. This review provides a comprehensive overview of transplant rejection with a particular focus on the pathophysiology and therapeutic landscape of cAMR. We highlight the role of plasma cell-driven alloantibody production and its susceptibility to endoplasmic reticulum (ER) stress, a pathway with potential for therapeutic intervention. Special attention is given to calcineurin inhibitors (CNIs), which, beyond their well-established T-cell inhibitory effects, exhibit differential impacts on ER stress and plasma cell viability. By delineating the mechanistic differences between cyclosporine and tacrolimus in regulating ER stress responses, we propose potential therapeutic implications for optimizing cAMR management. This review underscores the need for innovative strategies targeting plasma cell biology to improve long-term transplant outcomes.
Subjects
ER stress
calcineurin inhibitors
chronic alloantibody-mediated rejection
Publisher
MDPI AG
Type
journal article