Biologically Active CD40 Ligand Is Elevated in Sickle Cell Anemia

Abstract

Objective-After activation, platelets expose CD40 ligand (CD40L) on their surface, then subsequently release the inflammatory mediator as a soluble fragment (sCD40L). Because sickle cell anemia (SCA) is noted for both platelet activation and chronic inflammation, we asked whether platelet-released CD40L potentially plays a role in SCA. Methods and Results-ELISAs demonstrate that SCA patient plasma contains 30-fold more sCD40L than control plasma. Correspondingly, platelets from these patients contain less than half the CD40L found in control platelets. Platelets from patients in painful crises are further depleted of CD40L, with even higher plasma levels, suggesting a correlation to the patient's clinical state. In addition, elevated sCD40L correlates with increased tissue factor in SCA plasma. Blockage of the CD40L receptor CD40 reduces SCA plasma-induced production of tissue factor and endothelial intercellular adhesion molecule-1 (ICAM-1). Finally, sCD40L activity in SCA plasma is confirmed by its induction of B-cell proliferation. Conclusions-Platelet-derived sCD40L is elevated in SCA, further elevated in crises, and biologically active. The participation of sCD40L in SCA plasma-induced production of B cells, tissue factor, and ICAM-1 suggests that CD40L may contribute to the chronic inflammation and increased thrombotic activity known to occur in SCA.

Non-Conventional Pain Management for Sickle Cell Disease

“…However, most of these studies did not correlate with in vivo effect of the drugs on platelet activation with specific clinical endpoints [91]. Recent reports suggest that antiplatelet agents, particularly when administered at doses sufficient to inhibit platelet activation may be beneficial in preventing or treating vaso-occlusive complications in patients with SCD [95,91].…”

Vasoocclusion in Sickle Cell Anemia

“…7 Apropos of these observations, in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Lee and coworkers provide further evidence for a role of platelets in the pathophysiology of sickle cell anemia. 8 They report that plasma from patients with sickle cell anemia contained significantly increased amounts of soluble CD40 ligand (sCD40L) compared with plasma from normal controls and patients with anemia not attributable to sickle cell disease. Moreover, the amount of sCD40L increased during sickle cell crises, although not by a statistically significant amount.…”

Soluble CD40 Iigand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome

“…CD40-CD40L interaction constitutes one of the main pathways initiated by platelets that leads to inflammation, and is also implicated in the pathogenesis of atherosclerosis and other immuno-inflammatory diseases [14][15][16][17][18][19][20]. CD40L, a membrane glycoprotein belonging to the TNF superfamily, is expressed mainly by activated T cells and activated platelets [21,22].…”