Serum levels of soluble molecules associated with evasion of immune surveillance: a study in biliary disease.
BACKGROUND
Biliary carcinoma cells produce the transmembrane proteins, Fas, FasL, and RCAS1. It has been demonstrated that the Fas/FasL and RCAS1 systems induce apoptosis of activated immune cells and that the soluble isoforms of these proteins (sFas, sFasL, and sRCAS1) also exhibit this function.


METHODS
We measured serum levels of these soluble-types in patients with biliary disease by ELISA and investigated their clinical significance.


RESULTS
In some cases of cholangitis and autoimmune biliary disease, serum sFasL values were over 0.1 ng/ml but the protein was undetectable in any patients with biliary carcinoma. sFas levels were significantly higher in the autoimmune disease (mean, 6.83 ng/ml) and cancer (mean, 6.42 ng/ml) groups than in the cholangitis group (mean, 4.23 ng/ml) and normal controls (mean, 2.93 ng/ml). However, the sFas values in malignancy did not correlate with the progression of clinical stage. The percentage positive for serum sRCAS1 was 9.7% in benign disease but was 63.4% in cancer.


CONCLUSIONS
Our data suggest that serum sFasL in biliary disease may be derived predominantly from activated immune cells and not from cancer cells and that autoimmune biliary disease may be mediated by the Fas/FasL apoptotic system. sRCAS1 is highly tumor-specific and may be of value in the diagnosis of malignancy.
Enjoji
Munechika
M
Department of Medicine and Bioregulatory Science, School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. enjoji@intmed3.med.kyushu-u.ac.jp
Yamaguchi
Koji
K
Nakashima
Manabu
M
Ohta
Satoshi
S
Kotoh
Kazuhiro
K
Fukushima
Marie
M
Kuniyoshi
Masami
M
Tanaka
Masao
M
Nakamuta
Makoto
M
Watanabe
Takeshi
T
Nawata
Hajime
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology; D015551:Autoimmunity; D001424:Bacterial Infections / Q000097:blood / Q000276:immunology; D001661:Biliary Tract Neoplasms / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D015209:Cholangitis, Sclerosing / Q000097:blood* / Q000276:immunology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D012995:Solubility; D019014:fas Receptor / Q000097:blood*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D001798:Blood Proteins; C120762:EBAG9 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor