Serum Decoy Receptor 3 Research Articles

Serum Decoy Receptor 3 Is a Useful Predictor for the Active Status of Chronic Hepatitis B in Hepatitis B e Antigen-Negative Patients

Hepatitis B virus (HBV) infection is a global public health problem, because patients with chronic hepatitis B (CHB) may progress to liver cirrhosis and eventually evolve into hepatocellular carcinoma. Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily, and has been implicated in anti-apoptotic and anti-inflammatory pathways. In this study, we explored the clinical value of serum DcR3 in predicting the active status of CHB in hepatitis B e antigen-negative patients (active HBeAg (-) CHB), which was determined with ELISA. The serum level of DcR3 in active HBeAg (-) CHB patients (1.92 ± 0.68 ng/ml) was higher than that in healthy controls (0.80 ± 0.25 ng/ml, p < 0.0001) and that in inactive status of HBeAg (-) CHB (inactive hepatitis B surface antigen carrier, HBsAg-IaC) patients (0.95 ± 0.26 ng/ml, p < 0.0001). DcR3 level was correlated with HBV DNA level (r = 0.819, p < 0.0001) and alanine transaminase level (ALT, r = 0.704, p < 0.0001) in active HBeAg (-) CHB patients. The area under the Receiver Operating Characteristics curve of DcR3 for detecting the active status of HBeAg (-) CHB patients was 0.914 (95% confidence interval, 0.851-0.977). The optimal cut-off value for DcR3 to predict active HBeAg (-) CHB was 1.22 ng/ml, which had a sensitivity of 87.5% and a specificity of 84.4%. These results suggest that serum DcR3 level may be useful for detecting HBeAg (-) CHB in the active stage, which requires medical treatment.

High serum DcR3 levels are associated with the occurrence of peritonitis in patients receiving chronic peritoneal dialysis

BackgroundPeritoneal dialysis (PD)-related peritonitis is a serious complication that typically leads to hospitalization, catheter loss, and even mortality. Previous studies of the risk factors for peritonitis are discordant. To date, no biomarker associated with PD-related peritonitis has been investigated. However, it has been shown that serum decoy receptor 3 (DcR3) is a valuable marker in predicting the outcome of several inflammatory diseases. The aim of this study was to investigate whether serum DcR3 is a predictor of peritonitis in chronic PD patients. MethodsWe conducted a prospective cohort study of PD patients in the PD unit of a tertiary referral center from March 1 to November 30, 2007, and followed up until December 31, 2009. Clinical and laboratory parameters were recorded and serum DcR3 was measured to assess risk factors for developing PD-related peritonitis. ResultsA total of 77 patients (38 men and 39 women; mean age 58 ± 13 years) were enrolled in this study. The average time on PD was 24.5 months and 46 patients (60%) were diabetic. The mean follow-up duration was 499 ± 17 days. The rate of peritonitis incidence was 0.17 episodes per patient-year. Baseline serum DcR3 in 77 patients was 1.94 ± 1.23 ng/mL. Kaplan–Meier survival analysis showed that patients with serum DcR3 > 1.8 ng/mL had a higher risk of peritonitis than those with serum DcR3 < 1.8 ng/mL (p = 0.016). The Cox proportional hazard model further showed that high serum DcR3 (>1.8 ng/mL) was an independent risk factor for subsequent peritonitis (hazard ratio 3.61, 95% CI 1.17–11.08; p = 0.03). ConclusionSerum DcR3 was associated with increased risk of PD-related peritonitis.

Decoy Receptor 3, a Novel Inflammatory Marker, and Mortality in Hemodialysis Patients

Inflammation is closely associated with cardiovascular disease, the leading cause of mortality in patients with CKD. Serum decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily. CKD patients have higher levels of DcR3 than the general population, but whether DcR3 predicts mortality in CKD patients on hemodialysis has not been explored. DcR3 levels were measured in 316 prevalent hemodialysis patients who were followed up from November 1, 2004, to June 30, 2009, for cardiovascular and all-cause mortality. The baseline DcR3 concentration showed a strong positive correlation with inflammatory markers including high-sensitivity C-reactive protein, IL-6, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). During a follow-up period of 54 months, 90 patients died (34 cardiovascular deaths). Kaplan-Meier survival analysis showed higher cardiovascular and all-cause mortality in patients with higher DcR3 levels. The hazard ratios (95% confidence intervals) of the highest versus lowest tertiles of DcR3 were 2.8 (1.1-7.3; P for trend=0.04) for cardiovascular mortality and 2.1 (1.1-3.7; P for trend=0.02) for all-cause mortality, respectively. Based on the minimal increase in the area under the receiver operating characteristic curve from 0.79 to 0.80, the addition of DcR3 to established risk factors including VCAM-1, albumin, and IL-6 does not improve the prediction of mortality. Higher DcR3 levels strongly correlate with inflammation and independently predict cardiovascular and all-cause mortality in CKD patients on hemodialysis.

Clinical significance of serum decoy receptor 3 levels in patients with systemic sclerosis

Decoy receptor 3 (DcR3) is associated with autoimmunity and altered angiogenesis in certain pathological conditions. We herein measured serum DcR3 levels in 51 patients with systemic sclerosis (SSc) and 19 healthy controls and evaluated their clinical significance in this disorder. Serum DcR3 levels were significantly higher in diffuse cutaneous SSc (dcSSc) patients than in limited cutaneous SSc patients and in healthy controls. In dcSSc, serum DcR3 levels were significantly elevated in patients with disease duration of ≤6 years compared with healthy controls, but not in those with disease duration of >6 years. Serum DcR3 levels correlated negatively with the percentage of predicted diffusion lung capacity for carbon monoxide and positively with right ventricular systolic pressure. Furthermore, serum DcR3 levels positively correlated with C-reactive protein, erythrocyte sedimentation rate and immunoglobulin G. Collectively, the elevation of serum DcR3 levels is associated with the development of pulmonary arterial hypertension and systemic inflammation in SSc.

Serum decoy receptor 3, a potential new biomarker for sepsis

BackgroundSepsis, a common deadly systemic infection caused by a variety of pathogens, has some clinical symptoms similar to the systemic inflammatory response syndrome (SIRS), a whole-body non-infectious inflammatory reaction to severe insults, such as burn, trauma, hypotensive shock and so on. Treatment of sepsis depends mainly on anti-microbial, while remedy for SIRS might require steroids that could possibly enhance the spread of microbes. Unfortunately, it is very difficult to distinguish these two completely different serious conditions without blood culture, which takes days to grow and identify causative pathogens. We examined a biomarker, serum decoy receptor 3 (DcR3), was evaluated for its utility in the differential diagnosis between sepsis and SIRS. MethodsSerum DcR3 level in 118 healthy controls, 24 sepsis patients and 43 SIRS patients, was quantitatively measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe serum DcR3 was significantly increased in sepsis patients compared with SIRS patients and healthy controls (6.11±2.58ng/ml vs 2.62±1.46ng/ml, and 0.91±0.56ng/ml, respectively, p<0.001). The areas under the receiver operating characteristic curve of DcR3 for the normal vs. SIRS, normal vs. sepsis and SIRS vs. sepsis were 0.910 (0.870–0.950), 0.992 (0.984–1.000) and 0.896 (0.820–0.973), respectively. In addition, the DcR3 exhibited a positive correlation coefficient with APACHE II score, a most commonly used index for the severity of sepsis (r=0.556, p=0.005). ConclusionThe serum DcR3 has a potential to serve as a new biomarker for sepsis with its high specificity and sensitivity.

Serum decoy receptor 3 level: A predictive marker for nodal metastasis and survival among oral cavity cancer patients

Validating markers for prediction of nodal metastasis could be beneficial in treatment of oral cavity cancer. Decoy receptor 3 (DcR3), locus on 20q13, functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor (TNFR) family. This study analyzed the serum level of DcR3 in relationship to the clinical parameters of oral cavity cancer patients together with detection of DcR3 genomic copy number in primary and recurrent tumors. Elevated serum DcR3 was associated with nodal metastasis and worse prognosis. Gain of DcR3 copy number was detected in 17% of primary tumor tissue but not found in healthy areca chewers. Tissue from recurrent tumors showed more frequent DcR3 copy number alteration (48%) than the paired primary tumor tissue. Serum DcR3 level is a predictor for the nodal metastasis and survival among oral cavity cancer patients and the DcR3 copy number alteration could underlie oral carcinogenesis progression.

Decoy receptor 3: A pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases and cancer

Recently, several decoy molecules belonging to tumor necrosis factor receptor superfamily (TNFRSF) have been identified, including decoy receptor 1 (DcR1), decoy receptor 2 (DcR2), and decoy receptor 3 (DcR3). One of the tumor necrosis factor superfamily (TNFSF) members, TNF-related apoptosis-inducing ligand (TRAIL), binds to DcR1 and DcR2, which are membranous receptors with a truncated cytoplasmic domain, thus unable to transduce TRAIL-mediated signaling. In contrast to DcR1 and DcR2, DcR3 is a soluble receptor capable of neutralizing the biological effects of three other TNFSF members: Fas ligand (FasL/TNFSF6/CD95L), LIGHT (TNFSF14) and TNF-like molecule 1A (TL1A/TNFSF15). Since FasL is a potent apoptosis- and inflammation-inducing factor, LIGHT is involved in apoptosis and inflammation, and TL1A is a T cell costimulator and is involved in gut inflammation, DcR3 can be defined as an immunomodulator on the basis of its neutralizing effects on FasL, LIGHT, and TL1A. Initial studies demonstrated that DcR3 expression is elevated in tumors cells; however, later work showed that DcR3 expression is also upregulated in inflammatory diseases, where serum DcR3 levels correlate with disease progression. In addition to its neutralizing effect, DcR3 also acts as an effector molecule to modulate cell function via ‘non-decoy’ activities. This review focuses on the immunomodulatory effects of DcR3 via ‘decoy’ and ‘non-decoy’ functions, and discusses the potential of DcR3 as a biomarker to predict cancer invasion and inflammation progression. We also discuss the possible utility of recombinant DcR3 as a therapeutic agent to control autoimmune diseases, as well as the potential to attenuate tumor progression by inhibiting DcR3 expression.

High intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand TL1A in active ulcerative colitis

Decoy receptor-3 (DcR3) is a member of the TNF receptor superfamily of proteins, which has been implicated in anti-apoptotic and anti-inflammatory pathways, via binding to TL1A, LIGHT and Fas-L. The role of the TL1A/DcR3 ligand/receptor pair in ulcerative colitis (UC) has not been studied. We investigated the systemic (peripheral blood) and local (large intestine) expression of DcR3 and TL1A in 64 patients with UC and 56 healthy controls. DcR3 serum concentrations were highly elevated in patients with active UC (P<0.0001 vs. healthy controls). This elevation was clearly related to the presence of intestinal inflammation as it was less frequently observed in patients in remission (P=0.003 vs. active UC) whereas effective treatment resulted in disappearance or significant decrease of serum DcR3 (P=0.006 vs. pre-treatment). Furthermore, DcR3 mRNA transcripts were significantly elevated in inflamed areas of the colon (P=0.002 vs. non-affected of the same patient). In addition to DcR3 elevation, we found increased circulating levels of TL1A in patients with either active or inactive UC in comparison to healthy controls (P<0.001 for both). We conclude that elevated serum DcR3 may serve as an indicator of active colonic inflammation in patients with UC. TL1A/DcR3-mediated pathways may participate in the pathogenesis of UC.

The formation of osteoclasts in multiple myeloma bone disease patients involves the secretion of soluble decoy receptor 3

Soluble decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, has recently been reported to increase osteoclast (OC) differentiation. Its impact on the skeleton was reinforced by a study on DcR3 transgenic mice showing a decreased bone mass through the elevation of OC number, providing some initial evidence of DcR3 involvement in bone diseases. In this study we show that malignant plasma cells and T lymphocytes from myeloma patients directly produce DcR3, and this molecule supports the elevated formation of OCs in both peripheral blood and bone marrow from the patients. We also show that serum DcR3 levels in myeloma patients are significantly higher compared to controls.

Association of ascites and serum decoy receptor 3 (DCR3) levels with tumor infiltrating lymphocytes (TILS) and tumor vessels counts in epithelial ovarian cancer (EOC)

Association of ascites and serum decoy receptor 3 (DCR3) levels with tumor infiltrating lymphocytes (TILS) and tumor vessels counts in epithelial ovarian cancer (EOC)

Decoy receptor 3 is highly expressed in patients with rheumatoid arthritis

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a soluble receptor that binds to the TNF family including Fas ligand (Fas-L), LIGHT, and TL1A. DcR3 is mostly expressed in tumor cells and competitively inhibits the TNF family. We previously demonstrated that overexpressed DcR3 in rheumatoid synovial cells protects the cells from apoptosis in vitro. The objective of the study was to investigate DcR3 expression in serum and joint fluids of patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and to analyze the correlations with disease activities and TNFα expression. Sera and joint fluids were collected from patients with RA and OA. Expression of DcR3 in sera and joint fluids was measured by ELISA. The concentration of DcR3 in sera and joint fluids of RA patients was significantly higher than that in sera and joint fluids of OA patients. A correlation between serum DcR3 concentration and disease activity was not observed, but the serum DcR3 concentration was strongly correlated with the TNFα concentration. DcR3 was highly expressed in serum and joint fluids of RA patients.

Decoy receptor 3 is highly expressed in patients with rheumatoid arthritis

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a soluble receptor that binds to the TNF family including Fas ligand (Fas-L), LIGHT, and TL1A. DcR3 is mostly expressed in tumor cells and competitively inhibits the TNF family. We previously demonstrated that overexpressed DcR3 in rheumatoid synovial cells protects the cells from apoptosis in vitro. The objective of the study was to investigate DcR3 expression in serum and joint fluids of patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and to analyze the correlations with disease activities and TNFalpha expression. Sera and joint fluids were collected from patients with RA and OA. Expression of DcR3 in sera and joint fluids was measured by ELISA. The concentration of DcR3 in sera and joint fluids of RA patients was significantly higher than that in sera and joint fluids of OA patients. A correlation between serum DcR3 concentration and disease activity was not observed, but the serum DcR3 concentration was strongly correlated with the TNFalpha concentration. DcR3 was highly expressed in serum and joint fluids of RA patients.

Decoy receptor 3 expression during the menstrual cycle and pregnancy, and regulation by sex steroids in endometrial cells in vitro

Decoy receptor 3 (DcR3) is a soluble receptor belonging to the tumor necrosis factor receptor superfamily and can inhibit Fas ligand-induced apoptosis. DcR3 is related to carcinogenesis, but is found in human gestational tissues, where the function is uncertain. We aimed to determine DcR3 expression and regulation in endometrial cells in vitro, and throughout the menstrual cycle and pregnancy in vivo. Serum DcR3 levels were measured at various stages of the menstrual cycle (n = 40 women) and pregnancy (n = 20). DcR3 transcript and protein levels were analyzed in RL95-2 endometrial cells after treatment with estradiol (E(2)) (+/- anti-estrogen) and/or progesterone (+/- anti-progesterone). Finally, DcR3 protein and transcript were examined in decidua and chorionic villi from normal (n = 14) and anembryonic (n = 14) pregnancies. We identified a trend towards cyclic changes of serum DcR3 levels in the normal menstrual cycle, peaking at the mid-luteal phase, and relatively lower, more stable serum levels throughout normal gestation. DcR3 protein levels were higher in decidua than chorionic villi in normal pregnancy (P = 0.001), and levels in decidua were significantly lower in anembryonic than in normal pregnancies (P = 0.034). Physiologic concentrations of E(2) and/or progesterone stimulated DcR3 transcripts in RL95-2 endometrial cells. This study suggested that DcR3 expression varies during the menstrual cycle and is regulated by sex steroid hormones in vitro in endometrial cells. Human gestational tissues showed a differential production of DcR3, and decidual DcR3 protein was lower in anembryonic than normal pregnancies, suggesting an active role of DcR3 in the regulation of successful pregnancies.

Elevated serum decoy receptor 3 with enhanced T cell activation in systemic lupus erythematosus

Decoy receptor 3 (DcR3/TR6) is a decoy receptor for the Fas ligand (FasL) and can inhibit FasL-induced apoptosis. It has been reported recently that DcR3 can induce T cell activation via co-stimulation of T cells, suggesting that DcR3 may be involved in the pathophysiology of autoimmune diseases. This study aims to analyse the serum DcR3 in patients with systemic lupus erythematosus (SLE) and to investigate the role of DcR3 in the pathogenesis of SLE. Significantly elevated serum DcR3 was observed in SLE patients, and the mean serum DcR3 level was significantly higher for those with active disease [SLE disease activity index (SLEDAI) >/= 10] compared with that in patients with inactive disease (SLEDAI < 10). In addition to reducing activation-induced cell death in activated T cells via neutralization of the FasL, soluble DcR3-Fc enhanced T cell proliferation and increased interleukin-2 and interferon-gamma production via co-stimulation of T cells. Moreover, enhanced T cell reactivity to DcR3-induced co-stimulation was demonstrated in lymphocytes from patients with SLE, suggesting the elevated serum DcR3 may associate with enhanced T cell activation in vivo. These findings are the first to demonstrate that serum DcR3 concentrations are increased in SLE patients, and this may imply a possible role of DcR3 in the pathogenesis of SLE via enhanced T cell hyperreactivity and reduced apoptosis in activated T cells.

Serum Concentration of Soluble Decoy Receptor 3 in Glioma Patients Before and After Surgery

The suppression of immune responses in malignant gliomas is thought to be involved in glioma pathogenesis. The newly identified tumor-secreted soluble decoy receptor 3 (DcR3) can bind to the ligands CD95L and LIGHT, thereby neutralizing their pro-apoptotic actions. Little is known of the production of DcR3 by glioma cells. This study investigated the serum concentration of DcR3 in glioma patients before and after tumor removal. Blood samples were taken from 17 glioma patients and 10 control patients. The serum DcR3 concentration was measured using a DcR3 enzyme-linked immunosorbent assay. There was no statistically significant difference between preoperative (0.069 +/- 0.027 ng/mL) and postoperative DcR3 concentrations (0.068 +/- 0.022 ng/mL; p = 0.951). Similarly, there was no difference in preoperative DcR3 concentration between glioma patients (0.069 +/- 0.027 ng/mL) and controls (0.063 +/- 0.023 ng/mL; p = 0.106). Our study demonstrated no alteration in DcR3 concentration in glioma patients before and after tumor removal.