Serum Levels Of Receptor Research Articles

Assessment of Bone Morphogentic protein receptor 2 Level in Pulmonary Arterial Hypertension Disease

In the current study, Fifty six patients of Pulmonary arterial hypertension were admitted from Echocardiography unit and Najaf Cardiac Centre in Al-Sadder Teaching City in Al- Najaf province/ Iraq during September 2016 to February 2017,divided into seven groups:-First group according to gender (Male= 34 , Female = 22) Second group according to the type of disease ,primary included 20 patients and secondary 36 group , Third group according to Smoking included smokers 26 subjects and nonsmokers patients group included 30 subjects, Fourth group according to the type of secondary pulmonary hypertension ( Vulvular 24, Chronic Obstructive Pulmonary Disease 18 and Congenital 14) ,fifth group according to ages (30 – 39 year =12 ,40 – 49 year = 12 , 50 – 59 year= 12 , 60 – 69 year = 20) , six group according to Grades ([ Mild = 18 , moderate = 18 , severe; 20).The control group was composed of thirty healthy subject. The results of current study indicated, there were statistically significant decrease (p<0.05) in serum levels of Bone morphogenetic protein receptor 2 in patients of PAH in compared with healthy group. Also the results revealed a significant decrease (p<0.05) in BMPR2 in Females in compared with Males, Primary PAH than Secondary, Nonsmokers in compared with Smoker. And Chronic Obstructive Pulmonary Disease and Congenital in compared with Vulvular, Normal weight in compared with overweight and obese, 30-39 years in compared with other aged groups and in severe grades than Mild and Moderate. Conclusion: The current results concluded that BMPR2 is a marker for detection and diagnosis of Pulmonary arterial hypertension.

Serum Levels of Cytokines and Cytokine Receptors Are Associated with Outcome in Newly Diagnosed AML Patients

Background: Cytokines, cytokine receptors and adhesion molecules have been studied as markers of immune system activation in various diseases including AML/MDS. These factors form a dynamic network which affects AML cell susceptibility to chemotherapy. To provide more evidence of these interactions, we analyzed the serum levels of a broad panel of cytokines, cytokine receptors, matrix metalloproteinase-9 and soluble adhesion molecules.Aims: The aim of our study was to evaluate hypothesis that baseline serum levels of these factors are associated with relapse and overall survival (OS).Methods: A total of 65 AML patients (27 males, 38 females, mean age 53.7 ± 12.8, median 57.1 years) newly diagnosed in the period 2011 - 2014 were analyzed. All patients were Caucasian. Of these, 14 had better risk, 10 intermediate-1 risk, 13 intermediate-2 risk and 28 high risk AML according to ELN risk stratification (Döhner et al., Blood 2010). The NPM-1 was mutated in 16 cases, the FLT3-ITD was present in 15 cases. The secondary disease was present in 26 cases, 3 patients were BCR/ABL positive. Five patients with APL were treated with the PETHEMA regimen combining Idarubicin and All-trans retinoic acid (ATRA). All other patients were induced with "3+7" induction chemotherapy consisting of Cytarabin 100mg/m2 per day for 7 consecutive days and Daunorubicin 90mg/m2 for the first 3 days of therapy in younger patients. In patients aged ≥ 65 years, Daunorubicin 45-60mg/m2 was administered, depending on patient WHO performance status.We evaluated baseline circulating levels of the following factors: interleukins (IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-15), epidermal growth factor (EGF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-gamma (IFN-γ), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), matrix-metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), soluble IL-2 receptor-α (sIL-2Rα) and soluble receptors for IL-6 (sIL-6R) and TNF-α type I and II (TNFR-1,2), E-selectin (E-SEL), P-selectin (P-SEL), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). All biomarkers were measured by biochip array technology on Evidence Investigator analyzer (Randox). Statistical analysis was performed in R 3.1.2. Probability values (P) < 0.05 were considered statistically significant.Results: All evaluated analytes were independent of age, disease origin and ELN risk stratification. Relapse occurred in 34 cases with median of 516 days. Median follow-up was 627 days. Primary AML, normal karyotype and achieving of complete remission (CR) after induction therapy were associated with better relapse free survival (RFS), whereas higher TNFR-1, VEGF, IL-3, TNFR-2, NPM-1 and BCR/ABL were associated with inferior RFS. OS correlated with levels of IFN-γ, GM-CSF and TNFR-1. In multivariate analysis, primary AML, higher IL-10 and IL-15 were associated longer OS. Higher age, higher ELN risk and higher levels of TNFR-1, IL-3, IL-6, IL-8 and TNFR-2 were associated with inferior OS.Conclusions: Cytokines are an important part of cancer environment. In AML, some cytokines or their receptors may be informative for individual prognosis. The literature suggests association of IL-6 and IL-10 levels and OS (Correa et al., Cytokine 2013). Our data are in agreement with this finding, but revealed more cytokines and their receptors, especially TNFR-1, which were independently associated with relapse and OS. To confirm these findings, analysis in a larger cohort with longer follow-up should be performed.Acknowledgment:The work was supported by a specific research project "Analysis of defined prognostic factors in acute myeloid leukemia" (FMHS Hradec Kralove), by a long-term organization development plan 1011 (FMHS Hradec Kralove) and by MH CZ - DRO (UHHK, 00179906). DisclosuresNo relevant conflicts of interest to declare.

First trimester serum levels of the soluble transcobalamin receptor, holo-transcobalamin, and total transcobalamin in relation to preeclampsia risk

Background: Human placenta expresses CD320, a receptor that ensures the uptake of holo-transcobalamin (holoTC). Soluble CD320 (sCD320) is present in the circulation and its concentration increases during pregnancy.Aims: To investigate a possible association of sCD320, holoTC and total transcobalamin (TC) with the risk of subsequent preeclampsia using serum samples from asymptomatic first trimester pregnant women. Moreover, we aimed to establish reference intervals of the aforementioned biomarkers for first trimester pregnant women who remained healthy throughout pregnancy.Study design: This study was a retrospective case-control study that we performed on biobank serum samples. Cases (n = 50) and controls (n = 198) (matched for gestational age and date of sample collection) were asymptomatic women in early pregnancy [median (range) gestational age = 10 (8–12) weeks]. Cases developed preeclampsia while the controls remained normotensive throughout pregnancy. We measured the serum concentration of sCD320, holoTC, and total TC by using in-house ELISA methods.Results: First trimester median concentrations of sCD320, holoTC and total TC were not significantly different between cases and controls. The odd ratio for developing preeclampsia based on exposure to low or high levels of sCD320, holoTC or total TC at first trimester was not significant. The reference intervals (2.5–97.5% percentiles (median)) derived from the controls were 50–170 (90) pmol\\L for sCD320, 20–140 (70) pmol\\L for holoTC and 560–1300 (810) pmol\\L for total TC.Conclusions: The risk of preeclampsia is not predicted by first trimester serum concentrations of sCD320, holoTC or total TC. The first trimester reference intervals for the three parameters is reported.

Serum levels of soluble receptor for advanced end products are associated with restenosis occurrence in patients with diabetes mellitus after drug-eluting stent implantation

Serum levels of soluble receptor for advanced end products are associated with restenosis occurrence in patients with diabetes mellitus after drug-eluting stent implantation

Increased serum levels of vascular endothelial growth factor in pemphigus foliaceus patients with erythroderma

Erythroderma is a clinical skin syndrome shared by patients with cutaneous disorders of distinct aetiologies as a result of the combined actions of chemokines, adhesion molecules, and cytokines, such as vascular endothelial growth factor (VEGF). To evaluate the profile of serum levels of VEGF and soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) in pemphigus foliaceus (PF) patients with erythroderma. We conducted a retrospective study, which included (i) a chart review of all PF patients from the Autoimmune Blistering Clinic, University of Sao Paulo, Brazil, from January 1991 to December 2014, together with an evaluation of demographic variables, hospitalization duration and complications and (ii) analysis of the circulating VEGF and sVEGFR-1 levels in PF patients with erythroderma by ELISA. The controls included patients with pemphigus vulgaris or psoriasis. We observed higher serum VEGF levels in PF patients during erythroderma than during the non-erythrodermic phase. PF patients showed increased serum levels of sVEGFR-1 during the erythrodermic phase in comparison to controls. Interestingly, the sVEGFR-1 and antidesmoglein-1 levels were positively correlated during the non-erythrodermic period. Erythroderma, which represents one clinical form of PF, implies more severe outcomes. The circulating levels of VEGF, a potent endothelial activator, are increased in PF patients with erythroderma; this result suggests the contribution of the blood vessel endothelium to the pathogenesis of this clinical syndrome. Interestingly, our findings showed a positive correlation between the sVEGFR-1 and antidesmoglein-1 antibody levels, indicating a suppressive response to VEGF augmentation during the erythrodermic phase of PF.

Subcutaneous sarcoidosis: a clinical analysis of nine patients.

Subcutaneous sarcoidosis is the specific subset of cutaneous sarcoidosis frequently associated with systemic disease. However, the disease activity, severity, and prognosis have not yet been elucidated due to the limited number of reported cases. The purpose of this study was to identify the clinical, laboratory, and prognostic differences between subcutaneous sarcoidosis and other type of cutaneous sarcoidosis. All patients with sarcoidosis diagnosed histopathologically from 2000 to 2012 at our institution were enrolled. The clinical, laboratory, chest X-ray, and pulmonary function test results were retrospectively evaluated in the patients with cutaneous sarcoidosis. In the 130 patients with sarcoidosis, cutaneous sarcoidosis was diagnosed in 37 patients (28.4%), and 9 (6.9%) of these patients had subcutaneous sarcoidosis. The serum levels of soluble interleukin-2 receptor (sIL-2R) were significantly elevated in the group of patients with subcutaneous sarcoidosis in comparison to the patients with other types of cutaneous sarcoidosis, whereas there was no significant difference in the severity score between the two groups. Following a 2-year observation period, three patients were in remission, five patients demonstrated stable disease, and one patient had progressive disease. Subcutaneous sarcoidosis may be associated with the disease activity, although it was not found to be associated with the disease severity and it was not a predictive factor for the prognosis. Furthermore, the prevalence of subcutaneous sarcoidosis may be higher than that in previously reported series.

High cut-off dialysis in chronic haemodialysis patients reduces serum procalcific activity

Vascular calcification is enhanced in chronic dialysis patients, possibly due to the insufficient removal of various intermediate molecular weight uraemic toxins such as interleukins with conventional membranes. In this study, we assessed the modulation of in vitro vascular calcification with the use of high cut-off (HCO) membranes in chronic dialysis patients. In a PERCI trial, 43 chronic dialysis patients were treated with conventional high-flux and HCO filters for 3 weeks in a randomized order following a 2-period crossover design. After each phase, serum predialysis samples were drawn. Calcifying human coronary vascular smooth muscle cells (VSMCs) were incubated with the patient's serum samples. Calcification was assessed with alkaline phosphatase (ALP) and alizarin red staining. In the clinical trial, HCO dialysis reduced the serum levels of the soluble tumour necrosis factor receptor (sTNFR) 1 and 2, vascular cell adhesion molecule 1 (VCAM-1) and soluble interleukin-2 receptor (sIL2R). We therefore investigated the in vitro effects of these mediators on vascular calcification. VSMCs incubated with HCO dialysis serum showed a 26% reduction of ALP with HCO serum compared with high-flux serum. Alizarin was 43% lower after incubation with the HCO serum compared with the high-flux serum. While sIL2R and sTNFR 1 and 2 showed no effects on VSMC calcification, VCAM-1 caused a dose-dependent enhancement of calcification. The use of HCO dialysis membranes in chronic dialysis patients reduces the procalcific effects of serum on VSMC in vitro. The mechanisms of the strong effect of HCO on in vitro calcification are not completely understood. One factor may be lower levels of VCAM-1 in HCO serum samples, since VCAM-1 was able to induce vascular calcification in our experiments. Neither sTNFR 1, sTNFR 2 nor sIL2R enhance vascular calcification in vitro. Regardless of the mechanisms, our results encourage further studies of highly permeable filters in chronic dialysis patients.

Effect of S100A12 and soluble receptor for advanced glycation end products on the occurrence of severe acute pancreatitis.

To assess whether serum levels of S100A12 and soluble receptor for advanced glycation end products (sRAGE) could predict the severity of acute pancreatitis (AP). We conducted a non-interventional pilot study, including 74 AP patients and 28 healthy volunteers serving as controls. AP patients were further divided into the mild (MAP, n = 22), moderately severe (MSAP, n = 30) and severe (SAP, n = 22) groups. Peripheral blood samples were collected within 72 h after the onset of AP for the determination of S100A12, sRAGE and C-reactive protein (CRP) levels. The acute physiology and chronic health evaluation II (APACHE II) score, Balthazar computed tomography severity index (CTSI) were calculated at admission. S100A12 and sRAGE levels in SAP patient were significantly higher than in controls, MAP and MSAP patients. The receiver operating characteristic (ROC) curve analysis demonstrated the predictive ability of S100A12 [sensitivity 91%, specificity 81%, the area under the ROC curve AUROC 0.9047] and sRAGE (sensitivity 57%, specificity 100%, AUROC 0.8304) for evaluating the severity of AP. S100A12 and sRAGE were correlated with APACHE II and CTSI but not with CRP. This combination of new and traditional indicators had higher accuracy than traditional indicators alone. Specifically, S100A12 and sRAGE were positively correlated with the type of organ failure (respiratory and renal failure) and might distinguish transient from persistent organ failure at admission. S100A12 and sRAGE could be used as efficient biomarkers for the early identification of SAP.

Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats.

The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways.

Efficiency of AUY922 in mice with adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). ATLL is associated with poor prognosis mainly due to resistance to chemotherapy, which highlights the requirement for alternative therapies. The chaperone heat shock protein (HSP) 90 assist proteins involved in the onset and progression of ATLL. In the present study, the efficacy of a second generation HSP90 inhibitor termed AUY922 was investigated in ATLL. In vitro, AUY922 induced marked inhibition of cell viability in the HTLV-1-infected T-cell lines HUT-102 and MT-4. In immunodeficient mice bearing HUT-102 xenotransplants, AUY922 markedly retarded tumor growth, compared with the control group. Apoptosis was evident in hematoxylin and eosin stained- and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-labeled tissue sections from AUY922-treated mice. In addition, AUY922 significantly reduced the serum levels of the surrogate tumor markers soluble interleukin-2 receptor and soluble cluster of differentiation 30. Overall, the present results demonstrate that AUY922 has potent anti-ATLL activity, thus providing a rationale for continuing the clinical development of HSP90 inhibitors in clinical trials for the treatment of patients with ATLL.

Soluble urokinase plasminogen activator receptor (suPAR): Its relation to neurological outcome in patients with survived cardiac arrest

BackgroundHigh serum levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) have been associated with poor neurological outcome in patients after cardiac arrest (CA), but with inadequate and contradictive prediction values. The purpose of this study was to provide further evidence on the prognostic value of suPAR for the prediction of poor neurological outcome after initially survived CA. MethodsA total of 177 patients were prospectively enrolled in this cohort study. 85 patients with survived CA were included and the neurological outcome was assessed after 6months. 71 patients with ST-segmental elevation myocardial infarction (STEMI) and 21 healthy control patients served as comparative groups. ResultsThe serum suPAR levels on admission and the subsequent serum course were significantly higher in patients with CA as compared to STEMI and control patients. Furthermore, patients with poor neurological outcome showed significantly higher serum suPAR levels as compared to patients with good neurological outcome. By the use of ROC-curves and setting the specificities to 100%, inadequate sensitivities and cut-off values were calculated (day 2: sensitivity 21.1%, cut-off 10.2ng/dl, AUC 0.716). By setting the specificities to at least 80% the best prediction values could be calculated for day 2 with a sensitivity of 57.9% and a cut-off value of 5.3ng/dl. ConclusionsSuPAR serum levels in patients with poor neurological outcome were significantly higher as compared to patients with good neurological outcome. However, the prognostic value was low and inadequate because of a substantial overlap of serum suPAR levels between the outcome groups.

Effect of Ginkgo leaf extract and dipyridamole injection on serum and ascetic fluid levels of soluble triggering receptor expressed on myeloid cells-1 and plasma D-dimer in patients with spontaneous bacterial peritonitis

Objective To explore the effect of Ginkgo leaf extract and dipyridamole injection on serum and ascetic fluid levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and plasma D-dimer in patients with spontaneous bacterial peritonitis (SBP). Methods Totally 48 cirrhosis patients with SBP were randomly divided into therapeutic group (23 cases) and control group (25 cases). All the patients were given the standard treatment and low-salt diet. The patients in therapeutic group were treated with Ginkgo leaf extract and dipyridamole injection 25 ml, once every day for 2 weeks. The serum and ascetic fluid levels of sTREM-1 and plasma D-dimer were measured pre- and post-therapy, and clinical effects and side effects were observed. Results In the two groups, the levels of serum and ascetic fluid sTREM-1 and plasma D-dimer were decreased significantly post-therapy as compared with those pre-therapy [serum sTREM-1: (217.28±87.65) pg/ml vs. (52.02±16.36) pg/ml; ascetic sTREM-1: (218.76±69.38) pg/ml vs. (74.07±25.81) pg/ml; P 0.05). There was no obvious adverse drug reaction observed during the treatment in the two groups. Conclusion Ginkgo leaf extract and dipyridamole injection can down-regulate the serum and ascetic fluid levels of sTREM-1 and plasma D-dimer, relieve the local inflammatory reaction, and improve the response rate. Key words: Spontaneous bacterial peritonitis; Cirrhosis; Ginkgo Leaf extract and dipyridamole injection; Soluble triggering receptor expressed on myeloid cells-1; D-dimer

Racial-ethnic differences in midtrimester maternal serum levels of angiogenic and antiangiogenic factors

Little is known about racial-ethnic differences in the distribution of maternal serum levels of angiogenic and antiangiogenic factors and their associations with early-onset preeclampsia. We sought to investigate the distribution of midtrimester maternal serum levels of placental growth factor, soluble endoglin, and soluble vascular endothelial growth factor receptor 1 and their associations with early-onset preeclampsia in whites, Hispanics, and blacks. A population-based nested case-control design was used to identify cases and controls of white, Hispanic, and black origin from a 2000 through 2007 live-birth cohort in 5 southern California counties. Cases included 197 women (90 whites, 67 Hispanics, and 40blacks) with early-onset preeclampsia defined as hypertension and proteinuria with onset <32 weeks according to hospital records. Controls included a random sample of 2363 women without early-onset preeclampsia. Maternal serum specimens collected at 15-20 weeks' gestation as part of routine prenatal screening were tested for placental growth factor, soluble endoglin, and soluble vascular endothelial growthfactor receptor 1. Serum levels of the 3 factors were log-normally distributed. Adjusted natural logarithmic means were compared between cases and controls and between racial-ethnic groups. Odds ratios and 95% confidence intervals derived from logistic regression models were calculated to measure the magnitude of the associations. Cases showed lower adjusted logarithmic means of placental growth factor but higher adjusted logarithmic means of soluble endoglin than controls across all 3 groups (P < .05). Cases also had higher adjusted means of soluble vascular endothelial growth factor receptor 1than controls in whites (7.75 vs 7.52 log pg/mL, P < .05) and Hispanics (7.73 vs 7.40 log pg/mL, P < .05) but not in blacks (7.85 vs 7.69 log pg/mL, P= .47). Blacks were found to have higher levels of placental growth factor in both cases and controls when compared to whites and Hispanics (adjusted means: 4.69 and 5.20 log pg/mL in blacks, 4.08 and 4.78 log pg/mL in whites, and 3.89 and 4.70 log pg/mL in Hispanics, respectively, P < .05). Hispanic cases had the highest adjusted mean of soluble endoglin compared to white and black cases (9.24, 9.05, and 8.93 log pg/mL, respectively, P < .05). The weakest association of early-onset preeclampsia with placental growth factor and soluble endoglin was observed in blacks. The adjusted odds ratio per log pg/mL increase of the 2 analytes were 0.219 (95% confidence interval, 0.124-0.385) and 5.02(95% confidence interval, 2.56-9.86) in blacks in comparison to 0.048 (95% confidence interval, 0.026-0.088) and 36.87 (95% confidence interval, 17.00-79.96) in whites (P < .05) and 0.028 (95% confidence interval, 0.013-0.060) and 86.68 (95% confidence interval, 31.46-238.81) in Hispanics (P < .05), respectively. As for soluble vascular endothelial growth factor receptor 1, the association was not significantly different among the racial-ethnic groups. Racial-ethnic differences were observed in the distribution of midtrimester maternal levels of placental growth factor and soluble endoglin and in the associations with early-onset preeclampsia. These differences should be considered in future studies to improve etiologic and prognostic understanding of early-onset preeclampsia.

Two-Year Follow-up Study of Mycobacterium tuberculosis Antigen-Driven IFN-γ Responses and Macrophage sCD14 Levels After Tuberculosis Contact.

Clinical data regarding the prediction of active tuberculosis (TB) development in close TB contacts are scarce. To address this problem, we performed a 2-year follow-up study of Mycobacterium tuberculosis (M.tb) antigen-driven IFN-gamma responses and serum levels of soluble macrophage CD14 receptor in individuals with recent or prolonged M.tb exposure. Between June 2011 and June 2013, we studied 60 healthy Polish adults with recent household or long-term work TB contact and individuals without known M.tb exposure. All of them underwent baseline and repeated testing with IGRA (IFN-gamma release assay) and serum sCD14 ELISA quantification. Frequencies of IGRA results differed at the baseline and follow-up testing. IGRA reversions were noticed in almost one-third of Work TB Contacts and no participants from the Household TB Contact group. IGRA conversions were found in 40% of Household TB Contacts. No correlation between the IGRA result and the sCD14 level was observed. IFN-γ variability has important implications for clinical practice and requires caution in interpreting the results to distinguish new infections from nonspecific inter-individual variations in cytokine responses. The impairment of IFN-γ response in some individuals with prolonged M.tb exposure representing a resistant immune status does not allow considering IGRA results as reliable and credible. Monitoring the serum sCD14 level can reduce the likelihood of a false prediction of active TB development in close TB contacts showing an M.tb-specific increase in the IFN-gamma production in repeated IGRA testing.

Multiple immunological mechanisms of cancer cachexia in patients with solid tumors.

667 Background: Cancer cachexia is a mixed and multiple factorial condition and commonly seen in patients with advanced cancer, and has long been reported that host-immune function is critically participated. Chronic inflammation plays a key role in the progress of malignant diseases and has been reported to relate with immune suppression and nutritional impairment seen in patients with advanced diseases. Methods: Peripheral blood mononuclear cells (PBMC) were collected from 18 normal healthy volunteers and 112 patients with gastrointestinal cancer. These cells were used for the detection of MDSC (myeloid-derived suppressor cells: CD11b+CD14-CD33+) by flow cytometry. PBMC was also used for the PHA-blastogenesis of lymphocytes which is a marker of cell mediated immunity (stimulation indices: SI) and for the production assay of cytokines including IFN-G, IL-6 and IL-10. Serum levels of soluble cytokine receptors including sIL-2R and sTNF-R1, and anti-inflammatory molecules such as IL-10 and IL-1 receptor antagonist (IL-1RA) were also measured. For the evaluation of nutritional status, serum concentrations of rapid turnover protein (RTP) including prealbumin, transferrin and retinol binding protein was measured. NLR (neutrophil/lymphocyte ratio) was calculated and used as a marker of chronic inflammation. Results: The circulating levels of MDSC was significantly increased in esophageal, gastric and colorectal carcinomas than in normal volunteer and significantly inversely correlated with serum concentration of RTP and with SI, and correlated with markers for inflammation. The levels of sIL-2R and sTNF-R1 were increased in patients with gastric and colorectal and inversely correlated with the levels of RTP and SI. In patients with cachexia, serum concentrations of IL-10 were increased and the production of IFN-G was decreased. Conclusions: It is suggested that suppression of cell-mediated immune function exists in patients with cancer cachexia and the immunological mechanisms of nutritional damages in these patients are even partially driven by Th2-dominant condition of CD4(+) cells and MDSC. These complicated mechanisms are also involved in inflammation-related immunological condition such as SIRS and CARS.

Low expression of estrogen receptor β in T lymphocytes and high serum levels of anti-estrogen receptor α antibodies impact disease activity in female patients with systemic lupus erythematosus

BackgroundCurrent evidence indicates that estrogens, in particular 17β-estradiol (E2), play a crucial role in the gender bias of autoimmune diseases although the underlying molecular mechanisms have not yet been fully elucidated. Immune cells have estrogen receptors (ERs), i.e., ERα and ERβ, that play pro- and anti-inflammatory functions, respectively, and the presence of one estrogen receptor (ER) subtype over the other might change estrogen effects, promoting or dampening inflammation. In this study, we contributed to define the influences of E2 on T cells from female patients with systemic lupus erythematosus (SLE), a representative autoimmune disease characterized by a higher prevalence in women than in men (female/male ratio 9:1). Particularly, our aim was to evaluate whether alterations of ERα and ERβ expression in T cells from female SLE patients may impact lymphocyte sensitivity to E2 and anti-ERα antibody (anti-ERα Ab) stimulation interfering with cell signaling and display a direct clinical effect.MethodsSixty-one premenopausal female patients with SLE and 40 age-matched healthy donors were recruited. Patients were divided into two groups based on the SLE Disease Activity Index 2000 (SLEDAI-2K) (i.e., <6 and ≥6). ER expression was evaluated in T lymphocytes by flow cytometry, immunofluorescence, and Western blot analyses. Serum anti-ERα Ab levels were analyzed by enzyme-linked immunosorbent assay (ELISA). ER-dependent signaling pathways were measured by a phosphoprotein detection kit.ResultsIntracellular ERβ expression was significantly lower in T cells from patients with SLEDAI-2K ≥6 as compared with healthy donors and patients with SLEDAI-2K <6 and negatively correlated with disease activity. The expression of intracellular and membrane-associated-ERα was similar in SLE and control T cells. ER-dependent signaling pathways were activated in T cells from SLE patients with SLEDAI-2K ≥6, but not with SLEDAI-2K <6, when both membrane and intracellular ERs were stimulated by co-treatment with E2 and anti-ERα Abs.ConclusionsOur results demonstrate an altered ER profile in SLE patients, possibly contributing to SLE pathogenesis and interfering with clinical activity, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of disease activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-016-0057-y) contains supplementary material, which is available to authorized users.

Serum Levels of Interleukin-2 and Interleukin-2 Soluble Receptor in Patients with Vitiligo

Serum Levels of Interleukin-2 and Interleukin-2 Soluble Receptor in Patients with Vitiligo

Serum levels of soluble receptor for advanced glycation end product in type 2 diabetic patients: possible association with urinary albumin excretion

Diabetes is now the major cause of end-stage renal failure worldwide, both in developing and in developed nations. Hyperglycemia is still considered the principal cause of complications of diabetes because of the formation of sugar-derived substances called advanced glycation end products. The formation of advanced glycation end product is markedly accelerated in diabetes because of the increased availability of glucose. The receptor for advanced glycation end products (RAGE) has been shown to be involved in the pathogenesis of diabetic complications. The aim of this work was to assess the possible association between soluble receptor for advanced glycation end products (sRAGE) and urinary albumin excretion in type 2 diabetic patients as an early predictor of microvascular complications such as diabetic nephropathy. The present study was carried on 70 individuals: 10 healthy individuals as control, 20 diabetic patients with normoalbuminuria, 20 diabetic patients with microalbuminuria, and 20 diabetic patients with macroalbuminuria. All participants were subjected to estimation of sRAGE by the sandwich enzyme-linked immunosorbent assay technique together with routine laboratory investigations. The results of this study showed that all diabetic patients had a low level of serum RAGE compared with the control group. Furthermore, a characteristic trend was observed whereas three groups of diabetic patients showed a decrease in RAGE in parallel with the severity of renal involvement. From this point of view, stimulation of sRAGE production should be considered a potential therapeutic target in diabetic patients.

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.