Serum Soluble FasL Research Articles

Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study

BackgroundThe prognosis of patients with unresectable or metastatic biliary tract cancer (BTC) is unacceptably low. This study aimed to determine the efficacy, safety and predictive biomarkers of the immune checkpoint...

Serum soluble Fas ligand levels and peripheral blood lymphocyte subsets in patients with drug-induced maculopapular rashes, dress, and viral exanthemas

BackgroundFatty acid synthetase (Fas)/Fas ligand (FasL)-dependent apoptotic pathways have been reported as being involved in the pathogenesis of drug-induced maculopapular rashes. ObjectiveWe investigated serum soluble FasL (sFasL) levels and peripheral blood lymphocyte subtypes to discriminate maculopapular drug eruptions (MPDE) from viral exanthema (VE). Patients/methodsChildren with confirmed MPDE (group I), VE (group II), and drug rashes with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) (group III) were included. Serum sFasL levels and peripheral blood lymphocyte subtypes were analyzed in groups I–III on admission, and repeated twice (only once for group IV – controls). ResultsThere were no significant serum soluble FasL level differences among the groups for all the samples. In the initial samples, CD19+ cell numbers in group II were significantly higher than in group IV, and the CD4+/CD8+ ratio was higher than groups I and IV. In the second samples, CD4+ and CD19+ cell numbers were significantly higher in group II than group I. In the final samples, CD4+ cell numbers in group II were significantly higher than group I and group III. CD19+ cells numbers in group III were significantly lower than the other groups for all samples. ConclusionSerum sFasL levels were not found to be useful in discriminating viral exanthemas from other drug rashes. The significant differences between MPDE, VE, and DRESS were high CD4+ and CD19+ cell-count numbers in VE but low B-cell numbers in DRESS. This might be important for discriminating VE from DRESS, and the low B-cell count in early symptoms might be a useful predictor of DRESS development.

Serum soluble fas ligand levels and peripheral blood lymphocyte subtypes in patients with drug induced maculopapular rashes, dress and viral exanthemas

Background Fas/Fas ligand (FasL)-dependent apoptotic pathway was reported to be involved in the pathogenesis of drug induced maculopapular rashes (MPRs). In this study, we investigated serum soluble FasL level to discriminate drug-induced skin reactions from other clinically resembling skin diseases such as exanthematous viral infections. We also eveluated the role of T cells in various drug-induced diseases.

Serum levels of soluble Fas ligand in patients with silicosis.

Certain patients with silicosis have been reported to exhibit immunological abnormalities such as the appearance of antinuclear antibodies and the occurrence of autoimmune diseases. Fas ligand (FasL) is a type II membrane protein which induces apoptosis by binding to its membrane receptor, Fas. FasL is converted to a soluble form by a metalloproteinase-like enzyme. We have already found serum soluble Fas (sFas) levels in silicosis patients as well as in patients with systemic lupus erythematosus (SLE) to be significantly higher than those in healthy volunteers. To examine further the role of the Fas/FasL system in silica-induced immunological abnormalities, we investigated serum soluble FasL (sFasL) levels in silicosis patients with no clinical symptoms of autoimmune diseases, using ELISA for sFasL. Although the serum sFasL levels in patients with SLE were significantly higher than those in healthy volunteers and showed a slight positive correlation with serum sFas levels, those in silicosis patients exhibited no significant difference from those in healthy volunteers, and there was no correlation with serum sFas levels. However, sFasL levels were elevated in silicosis patients with slight dyspnoea or normal PCO2 among various clinical parameters of silicosis. It may be speculated that the immunological disturbances presented by the abnormalities of apoptosis-related molecules in silicosis patients do not occur with a similar degree of respiratory involvement. Further studies are required to clarify which kinds of factors are involved in silicosis patients who exhibit immunological abnormalities.

Lack of Correlation Between Clinical Characteristics and Serum Soluble Fas Ligand Levels in Patients with Multiple Myeloma

Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow and rarely cured by chemotherapy. Villunger et al. showed that the neoplastic plasma cells express Fas ligand (FasL), which transmits a signal of apoptosis upon ligation to Fas, and suggested that the FasL suppresses the T-cells activated against malignant cells, resulting in escape from tumour immunity. We examined serum soluble FasL (sFasL) levels in 35 multiple myeloma patients to evaluate the correlation between sFasL levels and clinical characteristics. The serum sFasL levels were not affected by the disease status, serum monoclonal protein levels, or other prognostic factors. We could not determine whether the expression of FasL is involved in the poor clinical course of the disease.

Fas and Fas ligand expression in cystic fibrosis airway epithelium

BACKGROUNDCystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defective expression of CFTR protein in epithelial cells. The main...

Inhibition of peripheral blood lymphocyte apoptosis by soluble fas ligand in patients with hepatocellular carcinoma.

We monitored apoptosis of peripheral blood lymphocytes (PBL) obtained from patients with various degrees of chronic viral hepatitis, including hepatocellular carcinoma (HCC), in vitro and quantitated the serum levels of soluble Fas ligand (FasL) by ELISA. There was no difference in mean percent PBL mortality. However, in HCC patients, the variance was significantly high (P<0.05), and, unexpectedly, a negative association was found between the PBL mortality and the serum soluble FasL levels (P=0.035). These results suggest the inhibitory effect of serum soluble FasL on apoptosis of PBL, which may explain the induction of immunological abnormalities with the development of HCC.

Increased Serum Soluble Fas Ligand Associated with Recurrent B-Cell Non-Hodgkin's Lymphoma after Autologous Peripheral Blood Stem Cell Transplantation

Fas-ligand (FasL) is a member of the tumor necrosis factor family and transmits apoptotic cell death signal by binding to its receptor, Fas. FasL is expressed on the cell surface of activated T-cell and natural killer (NK) cell. It has been shown that the FasL can be released from the cell surface by metalloproteinase. The serum soluble FasL (sFasL) is increased in some patients with NK cell lymphoma/large granular lymphocytic leukemia. We have recently seen a patient with recurrent B-cell lymphoma accompanied with an increased serum sFasL level after autologous peripheral blood stem cell transplantation. The sFasL was markedly decreased with the tumor regression induced by the chemotherapy. We present here the first case of an elevated serum sFasL level associated with B-cell lineage malignancy and discuss the possible clinical value of sFasL.