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3863 Hemoglobin Receptor CD163 As a Potential Biomarker of Hemolysis Induced Hepatobiliary Injury in Sickle Cell Disease

Program: Oral and Poster Abstracts
Session: 113. Sickle Cell Disease, Sickle Cell Trait and Other Hemoglobinopathies, Excluding Thalassemias: Basic and Translational: Poster III
Hematology Disease Topics & Pathways:
Research, Fundamental Science, Sickle Cell Disease, Hemoglobinopathies, Diseases
Monday, December 11, 2023, 6:00 PM-8:00 PM

Ramakrishna Ungalara1*, Omika Katoch, Ph.D2*, Tomasz Waldemar Kaminski, PharmD2* and Tirthadipa Pradhan-Sundd, PhD3

1University of Pittsburgh, Pittsburgh, PA
2Versiti Blood Research Centre, Milwaukee, WI
3Versiti Blood Research Institute, Milwaukee, WI

Sickle cell disease (SCD) associated chronic hemolysis promotes oxidative stress, inflammation and thrombosis leading to organ damage, including liver damage. Hemoglobin scavenger receptor CD163 plays a protective role in SCD by scavenging both hemoglobin-haptoglobin complexes and cell free hemoglobin. A limited number of studies in the past have shown a positive correlation of CD163 expression with poor disease outcomes in patients with SCD. However, the role and regulation of CD163 in SCD related hepatobiliary injury has not been fully elucidated yet. Here, we show that chronic liver injury in SCD mice and patients is associated with elevated levels of hepatic CD163. Hemolysis and increase in hepatic heme, hemoglobin, iron and haptoglobin levels elevate CD163 expression in the SCD mouse liver. Mechanistically we show that HO-1 positively regulates CD163 expression and that HO-1 and NRF2 form a complex with CD163 in the SCD liver. Finally, we demonstrate that blocking CD163 activity promotes hemolysis induced liver injury in SCD. These findings indicate that CD163 is a mediator and a potential biomarker of SCD associated hepatobiliary injury. Understanding the role of HO-1 in CD163 regulation may help identify novel therapeutic targets for hemolysis induced chronic liver injury.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH