Increased soluble and platelet-associated CD40 ligand in essential thrombocythemia and reactive thrombocytosis

International audienceCD40 ligand (CD40L) is expressed on activated CD4(+) T lymphocytes and at the activated platelet surface. A circulating soluble form of CD40L (sCD40L) is generated by the way of a proteolytic cleavage. We measured sCD40L in the plasma of either healthy subjects; patients with inflammatory disorders and low, normal, or high platelet count (reactive thrombocytosis); or patients with essential thrombocythemia (ET). A tight correlation was found between the platelet count and plasma sCD40L. ET patients had the highest levels of sCD40L. Platelet-associated CD40L was increased in ET and reactive thrombocytosis, conditions associated with increased platelet regeneration. Platelet-associated CD40L was released upon platelet activation. In conclusion, platelets appear as a reservoir of CD40L that may be a major contributor to circulating sCD40L. Platelet-associated CD40L may be a potential marker of platelet regeneration

Platelet-associated CD154 in immune thrombocytopenic purpura

International audienceCD40-ligand (CD154) is expressed on activated CD4+ T lymphocytes and is essential for the T cell-dependent activation of B lymphocytes. CD154 is also expressed at the activated platelet surface. In this study, we show that platelet-associated CD154 is increased in immune thrombocytopenic purpura (ITP), a disease characterized by an autoimmune response against proteins of the platelet membrane. CD154 and its messenger RNA were also present in increased amounts in the megakaryocytes of patients with ITP. We found that platelet-associated CD154 is competent to induce the CD40-dependent proliferation of B lymphocytes, and we observed an in vitro CD154-dependent production of antibodies to the GPIIb/IIIa complex (integrin alphaIIbbeta3) when platelets and peripheral blood B lymphocytes from ITP patients with circulating anti-GPIIb/IIIa antibody were cultured together. Therefore, platelet-associated CD154 expression is increased in ITP and is able to drive the activation of autoreactive B lymphocytes in this disease