Metabolic and Proteomic Divergence is Present in Spleens and Livers from Berkeley Sickle Cell Anemia and β-Thalassemia Mice.

Abstract

Sickle cell disease and β-Thalassemia are two of the most prevalent hemoglobinopathies worldwide. Both occur due to genetic mutations within the HBB gene and are characterized by red blood cell dysfunction, anemia, and end-organ injury. The spleen and liver are the primary organs where erythrophagocytosis, engulfing the red blood cells, occurs in these diseases. Understanding metabolism and protein composition within these tissues can therefore inform the extent of hemolysis and disease progression. We utilized a multiomics approach to highlight metabolomic and proteomic differences in the spleen and liver. The Berkley sickle cell disease (Berk-SS), heterozygous B1/B2 globin gene deletion (Hbb^Th3/+) a known β-Thalassemia model, and wildtype (WT, C57/Bl6) murine models were evaluated in this report. This analysis showed Berk-SS and Hbb^Th3/+ shared distinct antioxidant and immunosuppressive splenic phenotypes compared to WT mice with divergence in purine metabolism, gluconeogenesis, and glycolysis. In contrast, Berk-SS mice have a distinct liver pro-inflammatory phenotype not shared by Hbb^Th3/+ or WT mice. Together, these data emphasize that metabolic and proteomic reprogramming of the spleen and livers in Berk-SS and Hbb^Th3/+mice may be relevant to the individual disease processes.