Sickle cell anemia (SCA) is characterized by a number of variations in the clinical course of the disease process. A significant number of studies suggest that the inter-patient clinical variations may be a consequence of the relative proportion of dense sickle RBCs present in the circulation. Our recent studies demonstrate that dense sickle erythrocyte (RBC) subpopulations, contain several Ig-binding RBC subsets. The origins and pathophysiologic role of these circulating RBC subsets is unknown. To provide a bases for investigations which address these questions the present study will characterize the phenotypes of the individual dense sickle cell subsets by (a) determining the biochemical identity of Ig- binding membrane proteins; (b) defining correlations between non-Ig- binding RBC membrane markers and intracellular HbF; and (c) defining correlations between intracellular HbF and the identity of either IgG, IgM or IgA binding sites present on RBC components of specific Ig-binding dense subsets. These data are correlated with the proportion of reticulocytes, irreversibly sickled cells (ISCs) and nonISCs, content of each of the Ig-binding dense sickle cell subsets isolated by flow cytometric cell sorting; and compared with data derived from parallel analyses of low-density paired samples and dense normal(AA) RBCs. A separate set of studies will determine whether the proportionate distribution and phenotype of Ig-binding sickle RBC subsets is altered after hydroxyurea therapy, and identify specific sickle cell subsets most sensitive to this agent.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
1R03DK049232-01
Application #
2149888
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1994-09-30
Project End
1996-08-31
Budget Start
1994-09-30
Budget End
1995-08-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Southern California
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089