Role of circulating soluble CD40 as an apoptotic marker in liver disease.
OBJECTIVE
To measure levels of soluble CD40, a laboratory marker of apoptosis in patients with liver disease, determine its origin, and correlate the findings with disease activity and histology.


METHODS
Laboratory research study with comparison group.


METHODS
Liver Institute, Laboratory of HLA Typing and Histopathology Department, Rabin Medical Center, Israel.


METHODS
One hundred ten patients with liver disease and 20 healthy controls.


METHODS
Serum samples were collected from all patients; in addition, paired hepatic and portal vein samples were collected from 23 patients, and bile samples from 5 patients. Soluble CD40 was measured with an enzyme-linked immunosorbent assay. Apoptotic cells in liver tissue were identified by morphological criteria and quantified with the TUNEL assay.


RESULTS
Soluble CD40 concentration was significantly higher in patients with liver disease than controls (mean 112.9 +/- 197.2 pg/ml vs. 24.2 +/- 9.1 pg/ml, p = 0.0001), with highest levels in the chronic viral hepatitis group (mean 131.7 +/- 137.5 pg/ml, p = 0.0001). Levels of sCD40 were correlated with serum creatinine, alkaline phosphatase, alpha-feto protein, and the apoptotic index. In the 23 paired samples, CD40 level was higher in the hepatic vein (mean 74.9 +/- 114.5 pg/ml) than the portal vein (mean 51.6 +/- 67.9 pg/ml); it was highly detectable in bile (mean 115.6 +/- 119.6 pg/ml, p = 0.0123). Untreated patients with chronic viral hepatitis (B and C) had higher levels (mean 106.2 +/- 76.5 pg/ml) than treated patients (mean 59.3 +/- 68.6 pg/ml, p = 0.049).


CONCLUSIONS
Levels of soluble CD40 increase in different types of liver disease. It probably derives from the liver and is secreted into the bile. Levels correlate with the apoptotic index and are affected by antiviral treatment. Soluble CD40 may serve as a serum marker of apoptosis in liver disease.
Gastroenterology Unit, Golda Campus, Rabin Medical Center, Petah Tiqwa, Israel.
H
H
Schmilovitz-Weiss
A
A
Belinki
O
O
Pappo
J
J
Sulkes
E
E
Melzer
E
E
Kaganovski
B
B
Kfir
R
R
Tur-Kaspa
T
T
Klein
Z
Z
Ben-Ari
D017209:Apoptosis / Q000502:physiology*; D001646:Bile / Q000378:metabolism; D015415:Biomarkers; D019013:CD40 Antigens / Q000097:blood*; D005260:Female; D006503:Hepatic Veins / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000378:metabolism
D015415:Biomarkers; D019013:CD40 Antigens