Decreased expression of membrane ?4?1, ?5?1 integrins and transferrin receptor on erythroblasts in splenectomized patients with ?-thalassemia intermedia. Parallel assessment of serum soluble transferrin receptors levels

Dysfunction of cell membrane is a recognized consequence of the pathogenetic process underlying the β-thalassemia syndromes and it is reasonable to hypothesize that surface structures crucial for the development of erythroid lineage may also be affected. The study included six adult splenectomized patients with β-thalassemia intermedia. Expression of α4β1 integrin (CD49d/CD29), α5β1 integrin (CD49e/CD29) and transferrin receptor (CD71) on peripheral blood and bone marrow erythroblasts and on erythroid precursors grown in vitro was studied by flow cytometry and immunocytochemistry. Serum soluble transferrin receptor levels (sCD71) were also measured with enzyme-linked immunosorbent assay. In β-thalassemic patients, significant reduction of CD49d, CD29 and CD71 expression was found in peripheral blood nucleated red cells, compared to patients presenting with erythroblasts in the circulation because of other diseases. Marrow erythroblasts were also deficient for the same molecules against the erythroblasts in iron deficiency anemia. All molecules tested were greatly diminished on erythroid precursors developed in vitro from the patients' cells. Serum sCD71 levels were much higher in thalassemic patients in comparison to both patients with iron deficiency anemia and healthy individuals. The loss of certain integrins and CD71 from erythroid precursors in β-thalassemia intermedia could be attributed to a generalized membrane dysfunction, perhaps affecting the integrity of their transmembrane domains. The elevation of serum sCD71 levels may be the result of the increased red cell lineage turnover or, alternatively, may indicate increased shedding from the cells to prevent iron overload. In any case, further molecular study of the membrane components is warranted to provide a better understanding of the pathogenetic process in β-thalassemia syndromes.[PUBLICATION ABSTRACT]