Serum Levels Of Receptor Research Articles

Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Are Elevated in Severe Pre-Eclampsia

Background: Soluble urokinase plasminogen activator receptor (suPAR) is a novel marker for systemic inflammation both in infectious and in inflammatory diseases. Since pathophysiology of pre-eclampsia has been found to include impairment of maternal immune system, we wanted to explore serum level of suPAR in women with severe pre-eclampsia and whether it differs from healthy pregnancies and non-pregnant women. Methods: Serum samples of suPAR concentrations were analyzed from 10 patients with severe pre-eclampsia, 10 patients with uncomplicated pregnancies and 10 non-pregnant women. SuPAR concentrations were analyzed with enzyme-linked immune-sorbent assay (ELISA). Results: SuPAR levels were significantly higher in pre-eclampsia 3.5 ng/mL (2.4 - 4.8 ng/mL) compared to healthy pregnancy 2.0 ng/mL (1.7 - 2.6 ng/mL) (P =0.008) or non-pregnant women 2.3 ng/mL (1.9 - 2.9 ng/mL) (P = 0.015). Meanwhile, suPAR concentrations in healthy pregnant patients did not differ from non-pregnant women (P = 0.211). Conclusions: Serum suPAR levels are elevated in patients with severe pre-eclampsia implying that the systemic inflammatory response is enhanced in severe pre-eclampsia. J Clin Gynecol Obstet. 2016;5(4):101-105 doi: https://doi.org/10.14740/jcgo418w

The Majority of Myeloma Patients Are Vitamin D Deficient, Unrelated to Survival or Cytogenetics

▪Introduction: Since a link between solar radiation, vitamin D production, and decreased colon cancer mortality was established in 1980, there has been increasing interest in vitamin D and cancer, suggesting that higher vitamin D levels improve overall survival, specifically in breast and colorectal cancer (Maalmi H et al, Eur J Canc, May-2014, PMID 24582912), but also in follicular lymphoma (Kelly JL, J Clin Onc, 1-May-2015, PMID 25823738). In myeloma, largest published series is from the Mayo Clinic reporting on 148 newly diagnosed MM patients for which no survival association was found, but there were associations between low 25-OH-Vit D (<20 ng/mL) and higher serum CRP, serum creatinine, and ISS stage (Ng AC, Am J. Heme, Jul-2009, PMID 19415724); we wanted to expand on their trailblazing analysis. Cytogenetically high risk myeloma characterized by the amplification of 1q21 is associated with increased serum levels of soluble IL-6 receptor (sIL-6r) (Stephens OW, Blood, 2012, PMID 22072558) which may be associated with other markers of inflammation, e.g. CRP, creatinine, and b2microglobulin.Methods: The Buckeye Myeloma Registry (OSU 10115) opened in 2011 to enroll any patient with a plasma cell dyscrasia. Serum total 25-OH-Vitamin D was measured at the time of the initial clinic visit to the myeloma group at Ohio State.Results: Of a total of 843 patients, 115 (13.6%), 53 (6.3%) with SMM, and 675 (80.1%) with MM. In the 675 MM patients, the median age was 64 y.o. (range 28-95), 14.5% African-American and the remainder Caucasian, with 28.6% ISS stage 1, 48.7% ISS stage 2, 21.9% ISS stage 3, and 24.5% unknown. At diagnosis for the MM patients, 67% presented with lytic bone disease.Out of 675 MM patients, there were 52 (7.7%) patients with < 10 ng/mL 25-OH-Vit D, 394 (51%) with low vit D (10-30 ng/mL), and 229 (39%) for 25-OH-Vit D 30-100 ng/mL. There was no correlation between 25-OH-Vit D and BMI or creatinine, but there was a strong correlation with race (r=0.18, p<0.000026).Among the MM patients, log-rank [Mantel-Cox] analysis of overall survival with serum 25-OH-Vit D including all groups demonstrated no significant differences (p=0.9725) with only 101 events. There was no correlation between 25-OH-Vit D and the presence on CD138-selected FISH of 1q21 amplification (p=0.196), 17p (p53) deletion (p=0.68), or 13q deletion (p=0.812).Conclusion: The majority of myeloma patients are vitamin D deficient, but this was not associated with worsened overall survival or with high risk cytogenetics. Cox proportional hazards analyses of survival adjusted for significant univariate covariates will be presented at the meeting. Correlations with presence or absence of diffuse lytic bone disease, severity of renal insufficiency, and race will also be presented at the meeting. DisclosuresNo relevant conflicts of interest to declare.

The Majority of Myeloma Patients Are Hypogonadal but This Is Not Associated with High Risk Cytogenetics

Introduction: Hypogonadism, i.e. low total testosterone, is present in approximately a quarter of men older than 70 years (Harman SM et al, J. Clin Endo & Met, 2001, PMID 11158037 and Wu FCW et al, J Clin Endo & M et, 2008, PMID 18270261). Myeloma patients are known to suffer from fatigue and decreased functional performance, mood disturbances, and anemia; similar trends have been found in people with hypogonadism. Cytogenetically high risk myeloma characterized by the amplification of 1q21 is associated with increased serum levels of soluble IL-6 receptor (sIL-6r) (Stephens OW, Blood, 2012, PMID 22072558). We hypothesized that total testosterone levels will be associated with overall survival from the time of diagnosis, presence of 1q21 amplification by CD138-selected FISH, anemia, and anti-depressant use.Methods: The Buckeye Myeloma Registry (OSU 10115) opened in 2011 to enroll any patient with a plasma cell dyscrasia. Serum total testosterone was measured at the time of the initial clinic visit to the myeloma group at Ohio State. Less than 325 ng/dL was defined as the hypogonadal range, and testosterone was divided into <100 (group 1), 100-240 (group 2), 240-325 (group 3), and greater than 325 ng/dL (group 4), although normal testosterone decreases with age. Female patient testosterone levels were also analyzed and divided into <10 (group 1), 10-60 ng/dL (group 2), and >60 ng/dL (group 3). A retrospective chart review was initiated to review all myeloma patients with a serum testosterone drawn at the time of their initial clinic visit to OSU.Results: Among 418 male MM patients, median age was 65 y.o. (range 24-95), 86% were Caucasian and 14% African-American, and the distribution of ISS stage was 32% stage 1, 22% stage 2, and 19% stage 3 with 28% missing staging data. Cytogenetic data was missing from 28% of patients.Out of 418 male MM patients, 29 (7%) had serum testosterone <100, 202 (48%) with testosterone 100-240, 79 (19%) with testosterone 241-325, and 108 (26%) > 325 ng/dL. Out of 172 female MM patients, 44 (26%) had an undetectable serum testosterone, 120 (70%) with testosterone 10-60, and 8 (5%) with testosterone > 60. Among male MM patients, log-rank [Mantel-Cox] analysis of overall survival with serum testosterone including all 4 groups demonstrated no significant differences (p=0.917) with only 80 events. Among 275 male MM patients with cytogenetic information available, there was no correlation between presence of 1q21 trisomies or tetrasomies and overall survival (r=0.0714, p=0.238). There was a strong and expected correlation between testosterone and BMI (r=0.14, p=0.00468).Among 161 total female MM patients, log-rank analysis with serum testosterone including all 3 groups also demonstrated no differences (p=0.416) with only 29 events in total. Among 101 females with cytogenetic information, there was also no correlation with 1q21 amplification (r=0.0895, p=0.373).Conclusion: The majority of male MM patients (74%) have secondary hypogonadism and approximately half have total testosterone levels <240 ng/dL. Cox proportional hazards analyses of survival adjusted for significant univariate covariates will be presented at the meeting. Correlations with anemia and medication use (specifically opiates and anti-depressants) will also be presented at the meeting. DisclosuresNo relevant conflicts of interest to declare.

Serum Levels of sRAGE Are Associated with Body Measurements, but Not Glycemic Parameters in Patients with Prediabetes.

Our aim was to assess serum levels of the soluble receptor for advanced glycation end products (sRAGE) and to examine their association with anthropometric and metabolic parameters in patients with prediabetes and obese controls. The two study groups were composed of 42 patients with prediabetes and diabetic neuropathy and 42 age-, gender-, body weight (BW)-, and body mass index (BMI)-matched obese adults as the control group. Prediabetes was diagnosed by the following criteria issued by the American Diabetes Association: impaired fasting glucose [fasting plasma glucose (FPG) level of 100-125 mg/dL], impaired glucose tolerance (2 hr plasma glucose level of 140-199 mg/dL after a 75 grams oral glucose challenge), or a glycated hemoglobin (HbA1C) level of 5.7%-6.4%. There were no differences between the groups in terms of age, gender distribution, BW, or BMI. Despite these similarities, patients with prediabetes had higher FPG, HbA1c, and 2-hr postchallenge glucose levels, higher systolic and diastolic blood pressure, and larger waist and hip circumferences compared with the obese controls. Lipid measurements, complete blood counts, kidney and liver function tests, high-sensitivity C-reactive protein, and sRAGE levels were similar between the two groups. We found significant negative correlations between sRAGE levels and BW, BMI, waist and hip circumferences, waist-to-hip ratios, and low-density lipoprotein (LDL) cholesterol levels. There were no significant correlations with other parameters, including demographic, metabolic, and blood pressure measurements. In contrast to glycemic parameters, serum levels of sRAGE were negatively correlated with body measurements indicative of obesity in the prediabetic state. In addition, the negative correlation with LDL cholesterol levels suggests that sRAGE has a more robust association with metabolic syndrome than with prediabetes.

Abstract 12186: Therapeutic Effects of Blockade of IL-6/gp130 Signaling in Pulmonary Arterial Hypertension

Background: Interleukin (IL)-6 has been linked to the prognosis of pulmonary arterial hypertension (PAH). However, precise contributions of IL-6 and its signaling system to PAH progression is still obscure. Objectives: To study pathogenic roles of IL-6 cis- and trans-signaling in experimental and human PAH and to evaluate the translational potential of IL-6 signaling inhibition. Methods: We examined the global expression pattern of key actors of the IL-6 signaling in human lung tissues, blood samples and cultured pulmonary artery-smooth muscle cells (PA-SMCs) of 10 controls and 10 idiopathic PAH (IPAH) patients. In addition, two complementary animal models of pulmonary hypertension (PH) have been studied: the monocrotaline and SU5416 plus chronic hypoxia rat models. Results: In IPAH, serum levels of IL-6 and soluble IL-6 receptors (sIL-6R) proteins were higher than in control subjects. We also found stronger immunoreactivity for IL-6R, p-STAT3 and myeloid leukemia-cell protein 1 (Mcl-1, a downstream target of IL-6) in the media of remodeled pulmonary arteries and cultured PA-SMCs of IPAH patients compared with controls. These abnormalities in the IL-6/IL-6R signaling were also histologically found in the two rat models. Consistent with these findings, we also found that IL-6 with or without sIL-6R could substantially increase p-STAT3 and the anti-apoptotic Mcl-1 protein in cultured IPAH PA-SMCs compared with control cells. These effects were totally abolished in the presence of IL-6R neutralizing antibodies and an IL-6R antagonist. Finally, we found that daily treatment with IL-6R antagonist started 1 week after a subcutaneous monocrotaline injection substantially attenuates the abnormal increase in p-STAT3 and Mcl-1 and regresses established PH. Conclusions: We demonstrate here that anti-IL-6R strategies may represent promising novels anti-proliferative and anti-inflammatory approaches for treatment of PAH.

Clinical Significance of Serum IL-12 Level in Patients with Early Breast Carcinoma and Its Correlation with Other Tumor Markers.

AIM:To investigate the diagnostic significance of Interleukin 12 (IL-12) in breast cancer (BC) and its correlation with other tumor markers including cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and MMP9/TIMP1 ratio.METHODS:Serum levels of IL-12, tumor markers, and hormone receptors were measured in 92 BC and 56 benign lesion patients versus 40 healthy subjects. Clinical stage, tumor size, lymph node metastasis, grade, and histological type were recorded.RESULTS:BC patients have lower IL-12, but higher CA 15.3 and CEA than control group. High levels of serum IL-12 were associated with lymph node positivity and progesterone receptor negativity. IL-12 was significant lower in invasive ductal carcinoma (IDC) compared to non IDC histological type. IL-12 was higher in patients with higher stage and grade but the difference was not statistically significant. IL-12 correlates negatively with MMP9/TIMP1 ratio.CONCLUSION:IL-12 is less specific than CEA for screening early BC, but its correlation with tumor aggressiveness and progression markers may have a prognostic value.

Herbal formula menoprogen alters insulin-like growth factor-1 and insulin-like growth factor binding protein-1 levels in the serum and ovaries of an aged female rat model of menopause.

Menoprogen (MPG), a traditional Chinese medicine formula for menopause, improves menopausal symptoms; however, its mechanism remains unknown. Previous studies have shown that MPG is not directly estrogenic; thus, the goal of this study was to investigate the effects of MPG on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) levels in an aged female rat model of menopause. In a six-arm study, 14-month-old female Sprague-Dawley rats (n = 8 per arm) were randomly divided into the following groups: untreated aged, 17β-estradiol-treated aged (estradiol [E2]), and three arms with increasing doses of MPG (162, 324, or 648 mg/kg/d). The sixth arm contained 4-month-old female Sprague-Dawley rats as a normal comparison group. Four weeks after MPG or E2 administration, animals were killed after blood draws, and ovarian tissues were excised. Levels of E2 and progesterone (P4) were determined by radioimmunoassay. Serum and ovarian tissue levels of IGF-1, IGFBP-1, and IGF-1 receptor were determined by enzyme-linked immunosorbent assay. Compared with the normal group, aged rats had significantly reduced serum levels of E2, P4, and IGF-1, and increased serum and ovarian tissue levels of IGFBP-1. MPG restored serum IGF-1 and IGFBP-1 levels and down-regulated ovarian levels of IGFBP-1, which were closely related to increases in E2 and P4 levels in aged rats. No significant differences in either IGF-1 or IGFBP-1 were observed between the three doses of MPG. MPG exerts a direct in vivo effect on aged female rats by positively regulating serum and ovarian IGF-1 and IGFBP-1 levels.

GW26-e5439 Increased serum level of soluble VEGF receptor-1 is associated with low coronary collateralization in patients with stable coronary artery disease

The present study investigated whether serum levels of soluble vascular endothelial growth factor receptor (sVEGFR)-1, -2 and -3 are related to low coronary collateralization in patients with stable coronary artery disease. Serum levels of sVEGFR-1, -2, -3, VEGF and high-sensitivity C-reactive

Serum levels of soluble receptor for advanced glycation end products are associated with restenosis after drug-eluting stent implantation for stable angina pectoris

Aim: Some evidence points at the role of soluble receptor for advanced glycation end products (sRAGE) in restenosis pathogenesis. The objective of the present study was to define whether the occurrence of restenosis after drug-eluting stent (DES) implantation for stable angina pectoris (AP) is associated with different circulating levels of sRAGE.

A TCM herbal formula increases IGF-1 and IGFBP-1 levels in the sera and ovaries in an aged female rat model of menopause

Menoprogen (MPG), a TCM herbal formula improves menopausal symptoms in clinical trials, however its mechanism has remained elusive. Previous studies show that MPG is not directly estrogenic, thus the goal of this study was to investigate the effects of MPG on IGF-1 and IGFBP-1 levels in an aged female rat model of menopause. In a six-armed study, 14-month-old Sprague-Dawley (SD) female rats (n = 8 per arm) were randomly divided into an untreated aged group, an E2-treated aged group (17β-estradiol), and three arms with increasing doses of MPG groups (162, 324, or 648 mg/kg/day). The sixth arm contained four-month-old SD female rats as a normal comparison group. Four weeks after MPG or E2 administration, the animals were sacrificed after blood draws, and then ovarian tissues were excised. The levels of E2 and progesterone (P4) were determined by radioimmunoassay, and serum and ovarian tissue levels of IGF-1, IGFBP-1, and IGF-1 receptor (IGFR) were determined by ELISA. Compared with the normal group, the aged rats had significantly reduced serum levels of E2, P4, and IGF-1 and increased serum and ovarian tissue levels of IGFBP-1. MPG restored serum IGF-1 and IGFBP-1 levels and down-regulated the ovarian levels of IGFBP-1, which were closely related to increases of E2 and P4 levels in the aged rats. No significant differences were observed between the three doses of MPG for either IGF-1 or IGFBP-1. MPG has a direct in vivo effect in aged female rats by positively regulating serum and ovarian IGF-1 and IGFBP-1 levels.

Vitamin D Supplementation Increases Serum Levels of Soluble Receptor for Advanced Glycation End Products Among Women With Polycystic Ovary Syndrome [30

INTRODUCTION: To examine the effect of vitamin D3 supplementation on the changes in serum receptor for advanced glycation end products (sRAGE) and serum anti-Müllerian hormone (AMH) among vitamin D–deficient women with polycystic ovary syndrome (PCOS). METHODS: A total of 136 women with (n=68) or without (age-matched control; n=68) PCOS who were diagnosed with vitamin D deficiency were studied. All participants received supplemental oral vitamin D3 (50,000 international units/wk) for 8 weeks, followed by 1,000 international units vitamin D3 supplementation for 16 weeks. All women provided blood samples for the measurements of sRAGE, AMH, and other analytes at baseline and at the end of supplementation (24 weeks). RESULTS: In all participants, there was a negative correlation between body mass index and serum sRAGE levels (r=−0.46, P=.003). In women with PCOS, but not in those in the control group, vitamin D3 supplementation increased serum sRAGE (P<.001) and decreased serum AMH levels (P<.001). The increases in serum sRAGE were positively correlated with the increases in serum 25-hydroxyvitamin D after vitamin D3 supplementation in women with PCOS (r=0.72, P<.001). CONCLUSION: Vitamin D3 supplementation in women with PCOS showed a protective effect against the inflammatory action of advanced glycation end products by enhancing the circulating sRAGEs. The normalization in serum AMH induced by vitamin D3 therapy indicates a possible improvement in folliculogenesis.

Abstract 146: Third Intravenous Immunoglobulin Is An Effective Option For Kawasaki disease Patients Resistant To Cyclosporin A

Background: About 10-20% of patients with Kawasaki Disease (KD) who fail to respond to IVIG, show a high prevalence of CAL. The new guideline (2012) has proposed several options for second- and third-line therapy for patients resistant to IVIG. However, there are still no definite treatment options for refractory KD. We have reported that cyclosporin A (CsA) is a well tolerated, safe and promising option for patients resistant to IVIG. However, certain subgroups of such patients may also be resistant to CsA. In this study, we examined if a third course IVIG might be effective for patients resistant to CsA. Patients and Methods: Between April 2008 and May 2014, 42 Japanese patients who met the diagnostic criteria for KD and received CsA treatment were enrolled as study subjects. All patients were resistant to both initial (2 g/kg for 24 hours) and additional IVIG, and were then administered CsA orally (Neoral[[Unable to Display Character: &amp;#9415;]], oral solution, Novartis Pharma Co. Ltd., Tokyo, Japan). The initial dose of CsA was 4mg/kg/day, and it was divided into two equal daily doses every 12 hours. The dose of CsA was adjusted to between 4 and 8 mg/kg/day to maintain a trough level of 60-200 ng/ml by reference to clinical and laboratory data such as body temperature and C-reactive protein level. After the start of CsA treatment, if patients remained febrile for more than 5 days, or if fever returned after an afebrile period within 5 days, CsA treatment was judged to be ineffective, and the patients were then given a third course of IVIG. We analyzed some laboratory data between CsA effective group and CsA resistant group. Results: CsA treatment was judged to be ineffective in 14 of 42 (33%) patients. Eleven of those 14 patients received a third IVIG, and then, 8 (72.7%) patients of them became afebrile within 24hours. The other three patients became afebrile after a fourth IVIG. The serum levels of AST and soluble interleukin-2 receptor before the start of CsA treatment were significantly lower in CsA effective group than in CsA resistant group. Conclusion: A third course of IVIG is an effective option for KD patients who are resistant to CsA .

A case report of adrenocorticotropic hormone to treat recurrent focal segmental glomerular sclerosis post-transplantation and biomarker monitoring.

Background: Recurrent focal segmental glomerular sclerosis (rFSGS) in renal transplant recipients (RTR) is difficult to predict and treat. Early rFSGS is likely from circulating factors and preformed antibodies.Methods: We present the case of a 23-year-old white man who presented with rFSGS and acute renal failure, requiring dialysis 9-months after a 1-haplotype matched living-related transplant. We retrospectively analyzed serum samples from various clinical stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb), soluble urokinase-type plasminogen activator receptor (suPAR) serum level with suPAR-β3 integrin signaling on human podocytes, and angiotensin II type I receptor-antibody (AT1R-Ab) titer.Results: All biomarkers were abnormal at 1-year pre-transplant prior to initiation of dialysis and at the time of transplant. After initiation of hemodialysis, β3 integrin activity on human podocytes, in response to patient serum, as well as AT1R-Ab were further elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally high. One week after therapy with aborted plasmapheresis (secondary to intolerance), and high dose steroids, the Palb and suPAR-β3 integrin activity remained significantly positive. After 12-weeks of treatment with high-dose steroids, rituximab, and galactose, the patient remained hemodialysis-dependent. Three-months after his initial presentation, we commenced adrenocorticotropic hormone (ACTH, Acthar® Gel), 80 units subcutaneously twice weekly. Four-weeks later, he was able to discontinue dialysis. After 8-months of maintenance ACTH therapy, his serum creatinine stabilized at 1.79 mg/dL with <1 g of proteinuria.Conclusion: ACTH therapy was associated with improvement in renal function within 4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.

The combined serum levels of miR-375 and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer.

This study aimed to assess the applicability of miR-375 in combination with the soluble urokinase plasminogen activator receptor (suPAR) protein as a diagnostic and/or prognostic biomarker for prostate cancer (PCa) patients. miR-375 levels by qRT-PCR and suPAR levels by ELISA were evaluated in serum samples from 146 PCa patients, 35 benign prostate hyperplasia (BPH) patients and 18 healthy controls. Antigen levels of suPAR differed between healthy controls and PCa or BPH patients, whereas miR-375 levels differed between PCa and BPH patients or healthy controls (p < 0.001). Additionally, suPAR levels differed between the Gleason sum groups GS = 7 versus GS > 7, with higher levels in the latter group (p = 0.011), and miR-375 levels were higher in the tumor stage group T3-T4 compared with the T1-T2 group (p = 0.039). A high concentration of suPAR was associated with a poor disease-specific survival (DSS; p = 0.039). The combination of suPAR and miR-375 levels identified a patient group possessing high levels for both parameters. This was associated with a poorer 10-year overall survival (OS) and DSS, with a 6.38-fold increased risk of death and a 7.68-fold increased risk of tumor-related death (p = 0.00026 and p = 0.014; univariate Cox's regression analysis). In a multivariate Cox's regression analysis PCa patients with high levels of suPAR and miR-375 showed a 5.72-fold increased risk of death in OS (p = 0.006). In summary, the differences between the PCa/BPH/healthy control cohorts for either suPAR and miR-375 levels in conjunction with the association of combined high suPAR/miR-375 levels with a poor prognosis suggest a diagnostic and prognostic impact for PCa patients.

Serum soluble RAGE levels and carotid atherosclerosis: The Northern Manhattan Study (NOMAS)

BackgroundRecent cohort studies suggested that serum levels of soluble Receptor for Advanced Glycation End-products (sRAGE) are associated with the risk of cardiovascular disease. We hypothesized that sRAGE levels are associated with subclinical atherosclerosis in a racially and ethnically diverse population. Methods and results828 stroke-free participants from the Northern Manhattan Study (mean age 71.1 ± 8.7yrs; 64% Hispanic, 19% black, and 17% white) underwent high-resolution carotid B-mode ultrasound to measure carotid plaque (present in 62% of subjects) and intima-media thickness (IMT) (mean Total = 0.96 ± 0.10 mm). Serum sRAGE was measured by ELISA and associations tested between sRAGE with IMT and plaque presence. Soluble RAGE levels were not associated with plaque presence or IMT after adjusting for sociodemographic, vascular risk factors and medication use. Stratification by race-ethnicity did not reveal any associations with carotid IMT or plaque. ConclusionIn the present study, sRAGE levels were not associated with carotid atherosclerosis.

Elevated serum levels of decoy receptor 3 are associated with disease severity in patients with hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral infectious disease characterized by fever, hemorrhage and renal failure. HFRS has become a serious public health problem in China. Unfortunately, the pathogenesis of HFRS has not been completely clarified. The aim of this study is to investigate the changes of decoy receptor 3 (DcR3) and to further explore its potential roles in HFRS. The levels of serum DcR3 were measured by sandwich ELISA. We found serum DcR3 levels increased significantly, which reached peak value during the oliguric phase and in the critical group. Moreover, serum DcR3 levels were closely related to the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and parameters reflecting kidney injury including BUN, creatinine (Cr) and proteinuria. This study indicates that high levels of serum DcR3 have associations with the disease stages, severity and degree of kidney damage. Meanwhile, our results suggest that DcR3 may play a dual role in HFRS pathogenesis. First, DcR3 is involved in the inflammatory cascade response resulting in capillary permeability and kidney injury in the early stage. Secondly, HTNV infection induced DcR3 expression at the convalescent phase may act as a feed-back mechanism in anti-inflammatory response. Thus, a study of DcR3 is essential for a better understanding of HFRS pathogenesis.

Serum and synovial fluid levels of tumor necrosis factor-like ligand 1A and decoy receptor 3 in rheumatoid arthritis

ObjectiveTo measure the levels of Tumor necrosis factor (TNF)-like ligand 1A (TL1A) and decoy receptor 3 (DcR3) in serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA). To evaluate the effect of recombinant human (rh) TL1A on interleukin (IL)-17 production and IL-17mRNA expression. MethodsThe serum and SF levels of TL1A and DcR3, and the production of IL-17 by rhTL1A-treated PBMC were measured by enzyme-linked immunosorbent assay (ELISA). The expression of IL-17 mRNA by rhTL1A-treated PBMC was measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR). We also tested the change of TL1A and DcR3 level following TNF-α blockade therapy. ResultsSerum TL1A and DcR3 levels were higher in RA patients. This increase was more significant in RF and anti-CCP positive patients. TL1A and DcR3 levels were higher in SF samples than in paired sera. TL1A and DcR3 decreased after anti-TNF treatment. rhTL1A increased the production of IL-17 protein and the expression of IL-17mRNA. ConclusionTL1A and DcR3 may be of pathogenic and potentially of therapeutic importance in RA patients.

Conventional markers in determination of activity of sarcoidosis.

Currently, there are no objective criteria to determine sarcoidosis activity. The present study aimed to discover a sensitive serum marker that would determine the activity of sarcoidosis and can be used during disease follow-up. Forty-eight patients with sarcoidosis and twenty healthy volunteers as a control group were included in the study. On their control visits, the patients were divided into active and inactive groups based on their clinical, physiological, and radiological status. Angiotensin converting enzyme (ACE), adenosine deaminase (ADA), total IgE (T-IgE), C-reactive protein (CRP), serum amyloid-A (SAA), and soluble interleukin-2 receptor (sIL2R) serum levels and classical findings of activity were compared, and the utilization of these parameters as markers of activity was investigated. Thirty-nine cases were female (female/male: 39/9) and the mean age was 44.29±10.9years. Thirty-seven cases were active and 11 cases were inactive. Serum ACE, ADA, sIL2R, and SAA levels were significantly higher while T-IgE levels were lower in the sarcoidosis cases. A comparison of the markers between active and inactive cases showed that only SAA was significantly higher (p<0.001). sIL2R was elevated in cases with extra-pulmonary involvement (p<0.014). The area under the curve value was rather high for ADA (0.98 CI: 0.96-1.0); it also had high sensitivity (93.8%) and specificity (100%), and therefore had the highest diagnostic value (96.6%). The current study showed that SAA wil be helpfull for detecting the activity of srcoidosis, IL2R measurement in exploring the extra-pulmonary organ involvement.

Elevated Serum Levels of Soluble TNF Receptors and Adhesion Molecules Are Associated with Diabetic Retinopathy in Patients with Type-1 Diabetes.

Aims. To examine the association of the serum levels of TNF receptors, adhesion molecules, and inflammatory mediators with diabetic retinopathy (DR) in T1D patients. Methods. Using the multiplex immunoassay, we measured serum levels of eight proteins in 678 T1D subjects aged 20–75 years. Comparisons were made between 482 T1D patients with no complications and 196 T1D patients with DR. Results. The levels of sTNFR-I, sTNFR-II, CRP, SAA, sgp130, sIL6R, sVCAM1, and sICAM1 were significantly higher in the T1D patients with DR as compared to T1D patients with no complications. Multivariate logistic regression analysis revealed significant association for five proteins after adjustment for age, sex, and disease duration (sTNFR-I: OR = 1.57, sgp130: OR = 1.43, sVCAM1: OR = 1.27, sICAM1: OR = 1.42, and CRP: OR = 1.15). Conditional logistic regression on matched paired data revealed that subjects in the top quartile for sTNFR-I (OR = 2.13), sTNFR-II (OR = 1.66), sgp130 (OR = 1.82), sIL6R (OR = 1.75), sVCAM1 (OR = 1.98), sICAM1 (OR = 2.23), CRP (OR = 2.40) and SAA (OR = 2.03), had the highest odds of having DR. Conclusions. The circulating markers of inflammation, endothelial injury, and TNF signaling are significantly associated with DR in patients with T1D. TNFR-I and TNFR-II receptors are highly correlated, but DR associated more strongly with TNFR-I in these patients.

Soluble receptor for advanced glycation end products in critically ill patients and its associations with other clinical markers and 28-day mortality.

PurposeTo investigate the possible associations between serum levels of soluble receptor for advanced glycation end products (sRAGE) and specific clinical markers and prognosis in critically ill patients diagnosed with stress hyperglycemia.Patients and methodsA total of 70 critically ill patients and 25 normal controls were recruited for this study. Serum levels of sRAGE and advanced glycation end products (AGEs) were determined using enzyme-linked immunosorbent assay. Additional data on other clinical markers were obtained from patient records in the intensive care unit. Comparisons of sRAGE and AGEs levels between groups were assessed by t-test. The relationships between sRAGE and other clinical markers were assessed by Pearson’s correlation analyses and multiple linear regression analyses. Risk factors for prognosis, such as 28-day mortality were analyzed using logistic regression analysis.ResultsSerum sRAGE and AGEs levels were significantly higher in critically ill patients, compared to normal controls (P<0.05). The increase in serum sRAGE levels was significantly correlated with AGEs levels, interleukin-6 levels, and the sequential organ failure assessment score (P<0.01). Using multiple linear regression analysis, the association between AGEs and sRAGE remained significant after adjustment of other clinical factors. However, there were no significant correlations between sRAGE levels and patient outcome in these critically ill patients.ConclusionSerum sRAGE levels were significantly elevated in critically ill patients and positively correlated with higher AGEs levels, but sRAGE levels were not associated with increased mortality, suggesting sRAGE levels are not a predictor of prognosis in critically ill patients.