Detection of a soluble form of the human adhesion receptor lymphocyte function-associated antigen-3 (LFA-3) in patients with chronic liver disease.

BACKGROUND/AIMS: Multiple immune functions, such as cytotoxic reactions, B cell differentiation, and monocyte activation, are mediated via the adhesion receptor/ligand pairs CD2/lymphocyte function-associated antigen(LFA)-3 and LFA-1/ intercellular adhesion molecule(ICAM)-1. Since soluble forms of LFA-3 (sLFA-3) and ICAM-1 (sICAM-1) can interfere with these functions, we asked whether increased levels of sLFA-3 can be found in patients with different forms of chronic liver disease and/or hepatocellular carcinoma.

METHODS

sLFA-3 was measured in sera from 84 patients with chronic liver disease (39 with chronic viral liver disease, 30 with autoimmune liver disease, 12 with alcoholic cirrhosis, 3 with other causes of cirrhosis), 24 patients with hepatocellular carcinoma (15 with and 9 without cirrhosis), and 61 normal controls. From 36 of the patients with liver cirrhosis, arterial and hepatic venous serum samples were simultaneously obtained and tested for sLFA-3 and sICAM-1.

RESULTS

In comparison to controls, sLFA-3 levels were elevated in patients with liver cirrhosis due to autoimmune liver disease (p < 0.0001) and viral liver disease (p = 0.001), but not in patients with alcoholic cirrhosis. Increased sLFA-3 levels were also found in patients with hepatocellular carcinoma and liver cirrhosis. However, sLFA-3 was not significantly elevated in sera from patients with autoimmune liver disease, viral liver disease, and hepatocellular carcinoma without concomitant liver cirrhosis. No difference was found between arterial and hepatic venous serum levels of sLFA-3 and sICAM-1. sLFA-3 levels correlated positively with aspartate transaminase, alkaline phosphatase, bilirubin, sICAM-1, and inversely with albumin and cholinesterase.

CONCLUSIONS

Taken together, sLFA-3 serum concentrations of patients with liver cirrhosis due to autoimmune liver disease or viral liver disease and of patients with hepatocellular carcinoma and cirrhosis are significantly increased compared to controls. Elevated sLFA-3 and sICAM-1 levels might reflect the generalized inflammation in cirrhosis and by interference with cell-cell interactions sICAM-1 and sLFA-3 may limit the extent of inflammation.