Circulating Levels And Clinical Significance Of Soluble CD40 In Patients With Liver Disease

CD40, a type I transmembrane glycoprotein, belongs to the tumor necrosis factor receptor (TNFR) superfamily, and is expressed on a wide range of cells such as B cells, monocytes/macrophages, dendritic cells (DCs) .The interaction of CD40 with its ligand CD40L(CD 154),expressed predominantly on activated T cells,mast cells and basophils,is critical in the regulation of immune response and expression of inflammatory mediators,such as cytokines,chemokines and adhesion molecules.The soluble form of CD40(sCD40),which co-exists with the membrane-anchored form(mCD40) in vivo,is able to bind membrane CD40L and viewed as a natural antagonist of mCD40-CD40L interaction. Low levels of circulating sCD40 have been detected in the blood of normal donors and elevated levels of sCD40 have been reported in patients with renal failure,liver diseases,Alzheimer disease and hematologic malignancies, and its clinical signifances have been demonstrated, such as its values in diagnosis and prognosis of disease. Although it has been showed that activated B cells release sCD40 in vitro, the ability of other cell types to release sCD40 and its mechanisms of generation in vivo has not been established.In the current study we investigated circulating levels and clinical signifcance of sCD40 in patients with liver disease,and demonstrated the mechanisms of sCD40 generation in hepatocellular carcinoma(HCC).Soluble CD40 was measured with an enzyme-linked immunosorbent assay(ELISA).Compared with the low levels of sCD40 in the sera of normal controls,the sera levels of sCD40 were significantly higher in patients with different types of liver disease,including acute hepatitis,hepatitis gravis,hepatocirrhosis and primary carcinoma of the liver,and has negative correlation...