Characterization and statistical modeling of glycosylation changes in sickle cell disease.

Autor:	Ashwood HE; Versiti Blood Research Institute, Translational Glycomics Center, Milwaukee, WI., Ashwood C; Department of Biochemistry., Schmidt AP; Versiti Blood Research Institute, Translational Glycomics Center, Milwaukee, WI., Gundry RL; Department of Biochemistry.; Center for Biomedical Mass Spectrometry Research, and., Hoffmeister KM; Versiti Blood Research Institute, Translational Glycomics Center, Milwaukee, WI.; Department of Biochemistry., Anani WQ; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI; and.; Versiti Medical Sciences Institute, Milwaukee, WI.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2021 Mar 09; Vol. 5 (5), pp. 1463-1473.
DOI:	10.1182/bloodadvances.2020003376
Abstrakt:	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide. Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied. Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait. Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells. Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response. Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression. Our data provide detailed insights into glycan changes associated with sickle cell disease and refer glycans as potential therapeutic targets. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu