sCD40L

Soluble CD40 ligand (sCD40L), also known as soluble CD154, is the circulating form of the CD40 ligand, a transmembrane protein primarily expressed on activated CD4+ T cells and platelets. sCD40L is generated mainly by proteolytic cleavage of the membrane-bound ligand, and it is present in plasma and serum. Both the soluble and membrane-bound forms can bind the CD40 receptor on antigen-presenting cells, endothelial cells, B cells, and other cell types, modulating immune and inflammatory responses.

In immune signaling, CD40–CD40L interactions promote B cell proliferation and immunoglobulin class switching, dendritic cell maturation, and cytokine production. sCD40L can exert similar effects in a soluble form, particularly on platelets and endothelial cells, contributing to inflammation and thrombosis by inducing adhesion molecule expression, cytokine release, tissue factor, and procoagulant activity. The presence of sCD40L reflects platelet activation and inflammatory states in various contexts.

Cell sources and shedding: Activated T cells and platelets are major sources of sCD40L. Shedding is mediated by metalloproteinases such as ADAM10 and ADAM17, releasing the soluble form into circulation; other cell types may contribute under inflammatory conditions.

Clinical relevance: Elevated plasma sCD40L levels have been observed in cardiovascular disease, acute coronary syndromes, stroke, diabetes, and autoimmune diseases, and they are studied as biomarkers of platelet activation and thromboinflammation. The exact causal role remains under investigation, with evidence suggesting contributions to plaque instability and vasculopathy as well as inflammatory amplification in some contexts.

Measurement and considerations: Quantification is typically performed by immunoassay (ELISA); results can be affected by pre-analytical factors, including sample handling and platelet contamination, since platelets release sCD40L during processing. Understanding sCD40L continues to be relevant for immunology and cardiovascular medicine.