NEW CONCEPTS IN THE IMMUNOLOGY OF SICKLE-CELL DISEASE

Objective: Our objective is to review the role of adhesion molecules, cytokines, and inflammation in the abnormal adherence of sickle red bl ood cells to vascular endothelia in the pathogenesis of vascular compl ication in patients with sickle cell anemia. Data Sources: The MEDLINE database was used to review the hematologic, immunologic, and allergy literature in English with respect to the adhesion molecules involved in sickle hematopoiesis and vascular complications. Study Selection: Studies selected for review were those that identified the adhesion mo lecules involved in reticulocyte-endothelial adhesion and the influenc e that cytokines, infections, and atopy have upon the expression of th ese molecules. Results: In sickle cell disease, a constant low level o f inflammation caused by abnormal adhesion of sickle erythrocytes to e ndothelial cells in the microvasculature produces low-level tissue isc hemia. Allergic and infectious inflammations are likely to lead to inc reased sickle erythrocyte trapping in the microvascular endothelia whi ch progresses to vessel obstruction, end organ ischemic damage, and dy sfunction. Conclusion: The identification of underlying immune defects that predispose patients to infections and inflammation needs to be e mphasized. Anti-inflammatory medications, anti-adhesion molecule monoc lonal antibodies, and adhesion molecule binding-site analogs may have a future in the treatment of the acute vascular complications of sickl e cell disease.