CDDO-Imidazole regulates RBC alloimmunization to the KEL antigen by activating Nrf2
Che-Yu Chang1, Rosario Hernández-Armengol1, Kausik Paul1
1Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
Biorxiv : the Preprint Server for Biology
|April 16, 2025
Summary
Activation of the Nrf2 antioxidant pathway inhibits red blood cell alloimmunization. Nrf2 activators may offer a prophylactic strategy to prevent alloantibody responses in transfusion recipients.
Area of Science:
- Immunology
- Hematology
- Molecular Biology
Background:
- Red blood cell (RBC) alloimmunization can cause hemolytic transfusion reactions.
- Mechanisms inhibiting alloimmunization are crucial for developing prophylactic interventions.
- Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a master regulator of antioxidant pathways.
Purpose of the Study:
- To investigate the role of Nrf2 activation in regulating RBC alloimmunization.
- To determine if the Nrf2 activator CDDO-Im can inhibit anti-RBC alloantibody production.
Main Methods:
- Treatment of human macrophages and murine leukocytes with CDDO-Im.
- Assessment of Nrf2-activated gene expression and IFNα/β-stimulated gene expression.
- Transfusion of KEL antigen-expressing RBCs into wildtype and Nrf2-deficient mice, with or without CDDO-Im treatment.
Main Results:
- CDDO-Im induced Nrf2-activated gene expression and suppressed IFNα/β-stimulated gene expression.
- CDDO-Im treatment inhibited anti-KEL IgG production and improved RBC recovery in wildtype mice.
- These effects were abolished in Nrf2-deficient mice, demonstrating Nrf2-dependency.
Conclusions:
- Activation of the Nrf2 antioxidant pathway regulates RBC alloimmunization to the KEL antigen.
- Nrf2 activators may serve as a potential prophylactic intervention to inhibit alloimmunization in transfusion recipients.
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