Serum levels of soluble molecules associated with evasion of immune surveillance: a study in biliary disease

• Published in: Liver international 2004-08, Vol.24 (4), p.330-334
• Main Authors: Enjoji, Munechika, Yamaguchi, Koji, Nakashima, Manabu, Ohta, Satoshi, Kotoh, Kazuhiro, Fukushima, Marie, Kuniyoshi, Masami, Tanaka, Masao, Nakamuta, Makoto, Watanabe, Takeshi, Nawata, Hajime
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm - blood; Autoimmune Diseases - blood; Autoimmune Diseases - immunology; Autoimmunity; Bacterial Infections - blood; Bacterial Infections - immunology; Biliary Tract Neoplasms - blood; Biliary Tract Neoplasms - immunology; Biomarkers, Tumor - blood; Blood Proteins - metabolism; cholangiocarcinoma; cholangitis; Cholangitis, Sclerosing - blood; Cholangitis, Sclerosing - immunology; fas; fas ligand; Fas Ligand Protein; fas Receptor - blood; Female; Humans; Male; Membrane Glycoproteins - blood; Middle Aged; PBC; PSC; RCAS1; Solubility
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/j.1478-3231.2004.0931.x

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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.