CHARACTERIZATION OF MECHANISMS OF ERYTHROPHAGOCYTOSIS IN BETA-THALASSEMIC SYNDROMES: PROTEOMIC ANALYSIS AND APPLICATIONS

The project has the aim to give information about the mechanisms responsable of erythrophagocytosis and anemia in beta-thalassemic patients. We have previously demonstrated, in intermediate thalassemia (patients suffering of a form of thalassemia which do not require frequent transfusions), that erythrocytes are destroied by the immune system through the recognition of specific surface membrane structures. It was not previusly possible to describe the erythrocyte membrane alterations with sufficent detail to verify if it is possible to interfere with the erythrophagocytosis mechanism by specific molecules. In other words, it is not possible to plan the synthesis of molecules (peptides) which may interfere with the binding of the antibodies if their binding sites are not known. The recent development of sensitive and accurate technologies (proteomic technoilogies) allows fine protein characterizations on small blood samples. A complete set of proteomic technologies are available in our laboratory. In the present project, the auto-antibodies and the erythrocyte membrane complexes obtained from thalassemic patients and from two different mouse models of thalassemia will be isolated and further characterized. The project has the following aims:Molecular characterization of the binding sites of the auto-antibodies responsable for erythrophagocytosis in beta-thalassemiaCharacterization and quantification of the auto-antibodies present in thalassemic seraDevelopment of molecules interfering with the antigen-antibody binding to modulate erythrocyte removalDevelopment of a new diagnostic system to monitor auto-antibodies levels in patients