New concepts in the immunology of sickle cell disease

Our objective is to review the role of adhesion molecules, cytokines, and inflammation in the abnormal adherence of sickle red blood cells to vascular endothelia in the pathogenesis of vascular complication in patients with sickle cell anemia.

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.

Studies selected for review were those that identified the adhesion molecules involved in reticulocyte-endothelial adhesion and the influence that cytokines, infections, and atopy have upon the expression of these molecules.

In sickle cell disease, a constant low level of inflammation caused by abnormal adhesion of sickle erythrocytes to endothelial cells in the microvasculature produces low-level tissue ischemia. Allergic and infectious inflammations are likely to lead to increased sickle erythrocyte trapping in the microvascular endothelia which progresses to vessel obstruction, end organ ischemic damage, and dysfunction.

The identification of underlying immune defects that predispose patients to infections and inflammation needs to be emphasized. Anti-inflammatory medications, anti-adhesion molecule monoclonal antibodies, and adhesion molecule binding-site analogs may have a future in the treatment of the acute vascular complications of sickle cell disease.