Abstract
Soluble cluster of differentiation 40 (sCD40) is proteolytically cleaved from membrane-bound CD40 and binds to CD154, thereby inhibiting CD40-CD154-mediated immune responses. The aim of the present study was to clarify the role of sCD40 in chronic hepatitis B (CHB). The sCD40 levels in sera from 132 patients with CHB and 33 healthy individuals were retrospectively measured. sCD40 concentrations in patients with CHB were higher than those in healthy controls, and sCD40 levels correlated positively with serum levels of the liver dysfunction biomarkers alanine transaminase (ALT) and aspartate transaminase (AST). sCD40 concentrations increased with a rise in the severity of liver necroinflammation and fibrosis. Patients with >75% liver tissue staining positive for hepatitis B virus (HBV) antigen expression showed significantly lower sCD40 levels than those who stained negative for the HBV antigen. The area under the receiver operating characteristic curve of sCD40 was greater than that of ALT and AST; thus, sCD40 levels have a high diagnostic accuracy for detecting severe liver inflammation in patients with CHB, and could serve as an immunological marker of hepatic tissue injury.
Highlights
Cluster of differentiation (CD) 40 is a member of the tumor necrosis factor (TNF) receptor superfamily
The CD40‐CD154 co‐stimulatory pathway is involved in the pathogenesis of chronic hepatitis B (CHB) [16]
Intrahepatic CD40 expression has been shown to be upregulated on the surface of hepatocytes in CHB and to cause liver injury [23,24]
Summary
Cluster of differentiation (CD) 40 is a member of the tumor necrosis factor (TNF) receptor superfamily. It is expressed on the surface of immune cells, including B cells, monocytes, macrophages, dendritic cells (DCs) and activated T cells, as well as on the surface of non‐immune cells, such as epithelial, Key words: fibrosis, hepatocyte, immune, necroinflammatory endothelial and mesenchymal cells (including fibroblasts, myofibroblasts, synoviocytes and stellate cells) [1,2]. The binding of CD40 to its receptor on CD40‐expressing cells can lead to enhanced sCD40 release [7]. Circulating sCD40 levels are elevated in patients with chronic renal failure, chronic liver diseases, Alzheimer's disease, systemic sclerosis and hematological malignancies [10,11,12,13,14]
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