High Pentraxin 3 Research Articles

Pentraxin 3, a Predicator for 28-Day Mortality in Patients With Septic Shock

BackgroundUseful biomarkers that can serve as prognostic predictors are of great value in clinical practice because of the complex individual response to sepsis. Pentraxin 3 (PTX3), as a multifunctional pattern-recognition molecule, has been reported to be closely associated with the severity of infectious diseases in intensive care units (ICU). The aim of this study was to investigate whether PTX3 could serve as a potential prognostic biomarker in patients with septic shock. Materials and MethodsThis single-center prospective observational study was conducted during May 2012-May 2015 in the ICU of Taizhou People׳s Hospital. We compared the clinical data and laboratory tests in surviving and deceased patients with septic shock within 28 days from admission. Potential independent prognostic factors for septic shock were analyzed by using univariate and multiple Cox proportional hazards regression analyses. ResultsA total of 112 patients admitted to the ICU with septic shock were enrolled in our study with an overall 28-day mortality of 25.9% (29 of 112 patients). PTX3 level was the only independent risk factor for the 28-day mortality by univariate and multivariate Cox analysis (hazard ratio = 3.87; 95% CI: 1.66-8.81, P = 0.004). The deceased patients had significant higher levels of PTX3 at the 4 different points (baseline, day 1, day 2 and day 3) versus the survivors (P < 0.001). Results from Kaplan-Meier curves and log-rank test revealed that high PTX3 level (above the median value) was statistically associated with a lower 28-day survival rate (P = 0.014). ConclusionsThe baseline PTX3 level was an independent predictor for 28-day mortality in patients with septic shock.

Long-term prognostic value of elevated pentraxin 3 in patients undergoing primary angioplasty for ST-elevation myocardial infarction.

The prognostic value of pentraxin 3 (PTX3) has been documented in patients with acute coronary syndrome. However, its long-term prognostic value in acute ST-segment elevation myocardial infarction (STEMI) remains unclear. The aim of this study was to evaluate the prognostic value of PTX3 in patients with STEMI undergoing a primary percutaneous coronary intervention (PCI). We prospectively enrolled 499 consecutive STEMI patients undergoing primary PCI. The high-PTX3 group (n=141) was defined as having values in the third tertile (≥3.2 ng/ml) and the low-PTX3 group (n=358) included patients with values in the lower two tertiles (<3.2 ng/ml). The patients in the high-PTX3 group were older (mean age 54.3±11.8 vs. 58.5±13.1 years, P=0.002). Higher in-hospital cardiovascular mortality and 2-year all-cause mortality rates were observed in the high-PTX3 group (9.9 vs. 2.8%, respectively, P<0.001; 21 vs. 6.2%, respectively, P<0.001). In a Cox multivariate analysis, a high admission PTX3 value (>3.2 ng/ml) was found to be an independent predictor of 2-year all-cause mortality (odds ratio: 2.3, 95% confidence interval: 1.20-4.90, P=0.025). These results suggest that a high admission PTX3 level was associated with increased in-hospital cardiovascular mortality and 2-year all-cause mortality in patients with STEMI undergoing primary PCI.

Abstract 88: Pentraxin 3 in Coronary Artery Lesions in Kawasaki Disease

Although vascular inflammation is an important feature of Kawasaki disease (KD), the usefulness of local inflammatory markers as biomarkers for KD is unknown. Pentraxin 3 (PTX3), soluble lectin-like oxidized low density lipoprotein receptor 1 (sLOX-1) and matrix metraloproteinase-9 (MMP-9) are biomarkers of inflammation of vascular components. Objective: We tested whether plasma concentrations of PTX3, sLOX-1 or MMP-9 would be a useful biomarker for detecting high risk patient of coronary artery aneurysm (CAA) in KD and compared with serum level of interleukin-6 (IL-6) and IL-18. The ability of the assays to identify KD patients at risk for CAA was analyzed. Methods: PTX3, sLOX-1, MMP-9, IL-6 and IL-18 concentrations of 50 KD patients at different four clinical points were analyzed. Point A represented on admission; B, pre-IVIG; A+B, before IVIG; C, after IVIG; D, after fever resolution. Each concentration was compared with the rate of occurrence of CAA and IVIG unresponsiveness. Results: Each value was evaluated in 50 KD patients (2 with CAA, 48 without CAA). Three patients were treated without IVIG, 17 with one course of IVIG, and six with two IVIGs, two with three IVIGs, respectively. At the points A+B, C, D means for PTX3 were; 33.4, 11.7, 9.00 ng/ml, mean for MMP-9; 34.6, 19.2, 24.2 ng/ml, mean for sLOX-1; 3.82, 2.33, 2.25 ng/ml, respectively. Levels of PTX3 (p&lt;0.001) and MMP-9 (p&lt;0.05) were significantly higher in before IVIG than after IVIG; whereas levels of sLOX-1, as well as those of IL-6 and IL-18 were comparable between before and after IVIG. PTX3 were well correlated with IL-6 level (R2=0.73). Both cases with extraordinary high PTX3 levels at admission of 91.8 and 65.3 ng/ml were complicated with coronary artery aneurysms, even though they were treated by three courses of IVIG. The level of plasma PTX3 was significant related with the course numbers of IVIG (p&lt;0.05). Conclusion: Levels of PTX3 and MMP-9 appear to be associated with clinical course of KD. Levels of PTX3 were correlated with the severity of disease; how many doses of IVIG enough to resolve fever. An extraordinary high PTX3 level might be suggestive of the existence of CAA. These data suggest that PTX3 can be a candidate biomarker for prediction of unresponsiveness and CAA formation in patients with KD.

Gastric bypass–induced weight loss alters obesity-associated patterns of plasma pentraxin-3 and systemic inflammatory markers

BackgroundSystemic inflammation contributes to obesity-associated complications. The short pentraxin C-reactive protein (CRP) is a validated inflammatory marker, whereas long pentraxin-3 (PTX3) limits inflammation and is adaptively stimulated by proinflammatory cytokines in vitro. Severely obese (SO) patients (body mass index [BMI]>40] have the highest obesity-associated complications and increasingly undergo surgical treatment. SO-associated changes in plasma PTX3 and their interactions with systemic inflammation are, however, unknown. ObjectiveWe sought to determine potential alterations in plasma PTX3 and their associations with changes in inflammatory markers before and after weight loss induced by laparoscopic Roux-en-Y gastric bypass (LRYGB). SettingUniversity hospital in Trieste, Italy. MethodsPlasma PTX3, CRP, and cytokines, including tumor necrosis factor α and interleukin 6 were measured in (1) 24 individuals with severe, class III obesity (SO; age = 42±1 yr, female/male = 18/6, BMI = 45±1 kg/m2) before and 3, 6, and 12 months after LRYGB; and (2) age- and sex-matched normal-weight (N; n = 56, BMI = 22±.2 kg/m2) or class I obese individuals (O; n = 44, BMI = 31.2±.3 kg/m2). ResultsSO, but not O, had higher plasma PTX3 compared with N, associated with highest proinflammatory cytokines and CRP (P<.05 versus N-O). In all patients, plasma interleukin 6 and tumor necrosis factor α were associated positively with PTX3 (P<.05). Plasma CRP and proinflammatory cytokines declined during LRYGB-induced weight loss. In contrast, high PTX3 further increased and remained elevated (P<.05 versus basal). ConclusionsObesity level and energy balance modulate interactions between PTX3 and systemic inflammation. Elevated PTX3 is a novel, potentially adaptive alteration associated with proinflammatory cytokines in SO. Their differential changes conversely suggest circulating PTX3 as a novel negative inflammatory marker in SO undergoing LRYGB-induced weight loss.

The Effect of Intracoronary Stem Cell Injection on Markers of Leukocyte Activation in Acute Myocardial Infarction.

BackgroundBeneficial effects of stem cell treatment during acute myocardial infarction (AMI) have been suggested, but the effects on inflammation are controversial. The neutrophil cell markers pentraxin 3 (PTX3) and myeloperoxidase (MPO) are both reported to be elevated during AMI. We studied the effects of stem cell treatment in ST-elevation myocardial infarction (STEMI) on PTX3 and MPO levels.MethodsSubjects with STEMI undergoing percutaneous coronary intervention (PCI) were randomized to intracoronary injection of bone marrow cells (mBMCs) (n = 50) or controls (n = 50). Blood samples were drawn 1 day before mBMC injection (baseline), after 1 day, 3 days, 2 - 3 weeks and 3 months. Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were used for biochemical analysis. Myocardial necrosis was quantified by single photon emission computed tomography (SPECT) and creatine kinase MB (CKMB) levels.ResultsPTX3 and MPO levels did not differ between the groups at any time points. Within the mBMC group, overall changes in both variables were observed (P < 0.01), with decreased levels from baseline throughout. Within the control group, similar patterns were observed. The relative reduction of PTX3 from baseline to day 1 was significantly less pronounced in the mBMC group compared to controls (P = 0.002), whereas no differences in relative changes from baseline were observed for MPO. Plasma and gene expression levels of PTX3 in leukocytes correlated significantly at all time points (r = 0.379 - 0.448, P < 0.01, all). MPO was significantly correlated to baseline left ventricular ejection fraction (LVEF) (r = -0.229, P = 0.025) and peak CKMB (r = 0.200, P = 0.05).ConclusionsStem cell treatment had limited effect on plasma levels of PTX3 and MPO. The initially high PTX3 and MPO levels, the genetic regulation of PTX3 and the association between MPO and myocardial injury support the importance of neutrophil cell activation in STEMI.

Elevated Plasma Level of Pentraxin-3 Predicts In-Hospital and 30-Day Clinical Outcomes in Patients with Non-ST-Segment Elevation Myocardial Infarction Who Have Undergone Percutaneous Coronary Intervention

Objectives: This investigation explored the short-term prognostic value of pentraxin-3 (PTX3) levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI) treated by percutaneous coronary intervention (PCI). Methods: We measured plasma levels of PTX3 and other biomarkers in 525 PCI-treated NSTEMI patients (mean age, 57.7 years; 328 males). The associations of PTX3 levels with cardiac events and cardiac deaths occurring within 30 days of discharge were evaluated with multivariable Cox proportional hazard models. Results: Renal function, diabetes prevalence, systolic blood pressure, heart rate and ejection fraction differed significantly in the high PTX3 (≥3.0 ng/ml, n = 107) and low PTX3 (<3.0 ng/ml, n = 418) groups (all p < 0.05). Plasma PTX3 levels were correlated with high-sensitivity C-reactive protein, troponin T and N-terminal pro-B-type natriuretic peptide in NSTEMI patients (all p < 0.05). Kaplan-Meier analysis showed in-hospital and 30-day cardiac events and deaths were higher in the high PTX3 group (both p < 0.01). Elevated PTX3 was an independent predictor of 30-day cardiac events (95% CI 1.09-1.68; p = 0.006) and mortality (95% CI 1.18-2.15; p = 0.002). Conclusions: An elevated plasma level of PTX3 predicts 30-day cardiac events and mortality in PCI-treated NSTEMI patients.

Pentraxin-3 as a prognostic marker in patients with small-cell lung cancer.

The aim of this study was to determine the incidence and role of pentraxin-3 (PTX-3) overexpression as a predictive/prognostic marker in small-cell lung carcinoma (SCLC). We performed a retrospective study on subjects with a biopsy-proven diagnosis of SCLC. A chart review for demographic and clinical data was performed on patients with SCLC diagnosed between 2005 and 2008. PTX-3 overexpression was evaluated using immunohistochemistry performed on archival paraffin-embedded specimens. 125 patients with SCLC were identified (23 females, 102 males; median age 62.91±8.55 years, range 37-82) all of whom had adequate tissue specimens available for PTX-3 testing. High PTX-3 expression was detected in 25.6% SCLCs and was significantly associated with male gender and smokers. Moreover, elevated PTX-3 levels were correlated with reduced overall (OS) and disease-free survival, and were an independent negative prognostic factor for OS in SCLC. Our findings suggest that high PTX-3 expression appeared to correlate with aggressive behavior in SCLC, and it may be a useful prognostic marker for SCLC patients and a potential molecular target for SCLC treatment.

Pentraxin 3 concentrations of the mothers with preterm premature rupture of membranes and their neonates, and early neonatal outcome

Background: Pentraxin 3 (PTX3) is an acute phase reactant which has been used to detect intra-amniotic infections (IAI) in pregnancy, but the prognostic value of PTX3 concentrations on neonates has not been studied. We aimed to investigate the relationship between maternal PTX3–neonatal PTX3 concentrations and early neonatal outcome.Methods: The mothers diagnosed with preterm prelabor rupture of membranes (PPROM) (n = 28) and their preterm infants (n = 28) were included in the study. PTX3 concentrations were studied in plasma in the maternal peripheral blood and umbilical/peripheral vein in the neonates. The relationship between the mPTX3–nPTX3 concentrations and neonatal outcome were investigated using non-parametric tests and binary logistic regression analysis.Results: The mean mPTX3 concentration was 10.35 ± 7.82 μg/L. Ten (35.7%) of all mothers were within the normal range and 18 (64.3%) in high percentile (≥97.5 percentile). There was no relation between mPTX3 concentrations and clinical or histologic chorioamnionitis, latency of PPROM, and early neonatal outcome. Mean nPTX3 concentrations was 9.18 ± 7.83 μg/L and high nPTX3 concentrations were detected in five (17.8%) neonates. nPTX3 concentrations were inversely correlated with gestational age and correlated with rate of intraventricular hemorrhage (IVH) and mortality. Neonates with high nPTX3 concentrations also have lowered APGAR scores, increased rate of respiratory distress syndrome, clinical sepsis, IVH, necrotizing enterocolitis and prolonged NICU stay.Conclusion: High PTX3 concentrations of the newborns are associated with some worsened early neonatal outcome including lower gestational age at delivery, increased rate of IVH and mortality. Maternal PTX3 concentrations are not an adequate marker in defining clinical or histologic chorioamnionitis and early neonatal outcome.

Three-month variation of plasma pentraxin 3 compared with C-reactive protein, albumin and homocysteine levels in haemodialysis patients.

BackgroundInflammatory markers vary considerably over time in haemodialysis (HD) patients, yet the variability is poorly defined. The aim of the study was to assess changes of plasma levels of pentraxin-3 (PTX-3), C-reactive protein (CRP), albumin and homocysteine (Hcy) over 3 months and the association between the changes in these biomarkers and mortality.MethodsIn 188 prevalent HD patients, inflammatory markers were measured at inclusion and after 3 months. Mortality was recorded during a median follow-up of 41 months. The changes of the biomarker levels were categorized according to change in tertile for the specific biomarker. The variation was calculated as the intra-class correlation (ICC). Mortality was analysed by Kaplan–Meier and Cox proportional hazards model. The predictive strength was calculated for single measurements and for the variation of each inflammatory marker.ResultsThe intra-individual variation (low ICC) was largest for PTX-3 [ICC 0.44; 95% confidence interval (CI): 0.33–0.55], albumin (ICC 0.58; 95% CI: 0.49–0.67) and CRP (ICC 0.59; 95% CI: 0.51–0.68) and lowest for Hcy (ICC 0.81; 95% CI: 0.77–0.86). During follow-up, 88 patients died.ConclusionsPTX-3 measurements are less stable and show higher variation within patients than CRP, albumin and Hcy. Persistently elevated PTX-3 levels are associated with high mortality. Moreover, in multivariate logistic regression we found that stable high PTX-3 adds to the mortality risk, even after inclusion of clinical factors and the three other biomarkers. The associations of decreasing albumin levels as well as low Hcy levels with worse outcome reflect protein-energy wasting.

Monocyte activation, brain-derived neurotrophic factor (BDNF), and S100B in bipolar offspring: a follow-up study from adolescence into adulthood.

There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with bipolar disorder. Bipolar offspring, from the prospective Dutch bipolar offspring study (n=140), were evaluated cross-sectionally within a longitudinal context at adolescence, young adulthood, and adulthood. We examined the expression of 44 inflammation-related genes in monocytes, the cytokines pentraxin 3 (PTX3), chemokine ligand 2 (CCL2), and interleukin-1β (IL-1β), and brain-derived neurotrophic factor (BDNF) and S100 calcium binding protein B (S100B) in the serum of bipolar offspring and healthy controls. During adolescence, bipolar offspring showed increased inflammatory gene expression in monocytes, high serum PTX3 levels, but normal CCL2 levels. BDNF levels were decreased, while S100B levels were normal. During young adulthood, monocyte activation remained, although to a lesser degree. Serum PTX3 levels remained high, and signs of monocyte migration became apparent through increased CCL2 levels. BDNF and S100B levels were not measured. At adulthood, circulating monocytes had lost their activation state, but CCL2 levels remained increased. Both BDNF and S100B were now increased. Abnormalities were independent of psychopathology state at all stages. This study suggests an aberrant neuro-immune state in bipolar offspring, which followed a dynamic course from adolescence into adulthood and was present irrespective of lifetime or future mood disorders. We therefore assumed that the aberrant neuro-immune state reflects a general state of vulnerability for mood disorders rather than being of direct predictive value.

Long Pentraxin PTX3 Exacerbates Pressure Overload–Induced Left Ventricular Dysfunction

BackgroundLeft ventricular hypertrophy is enhanced by an inflammatory state and stimulation of various cytokines. Pentraxin 3 (PTX3) is rapidly produced in response to inflammatory signals, and high plasma PTX3 levels are seen in patients with heart failure. This study aimed to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction with respect to pressure overload.Methods and ResultsPTX3 systemic knockout (PTX3-KO) mice, transgenic mice with cardiac-specific overexpression of PTX3 (PTX3-TG), and the respective wild-type (WT) littermate mice were subjected to transverse aortic constriction (TAC) or a sham operation. Cardiac PTX3 expression increased after TAC in WT mice. In vitro, hydrogen peroxide induced the expression of PTX3 in both cardiac myocytes and cardiac fibroblasts. Recombinant PTX3 phosphorylated extracellular signal–regulated kinase 1/2 (ERK1/2) in cardiac fibroblasts. Phosphorylation of cardiac ERK1/2 and nuclear factor kappa-B after TAC was attenuated in the PTX3-KO mice but was enhanced in the PTX3-TG mice compared with WT mice. Interleukin-6 and connective tissue growth factor production was lower in the PTX3-KO mice than in the WT mice, but this was augmented in the PTX3-TG mice than in the WT mice. Echocardiography revealed that adverse remodeling with left ventricular dysfunction, as well as with increased interstitial fibrosis, was enhanced in PTX3-TG mice, while these responses were suppressed in PTX3-KO mice.ConclusionThe local inflammatory mediator PTX3 directly modulates the hypertrophic response and ventricular dysfunction following an increased afterload.

Pentraxin 3 (PTX3) Is Associated with Severe Sepsis and Fatal Disease in Emergency Room Patients with Suspected Infection: A Prospective Cohort Study

BackgroundEarly diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection.MethodsThe study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA).ResultsThe median PTX3 levels in groups 1–5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (p<0.001). The median PTX3 concentration was higher in severe sepsis patients compared to others (16.7 vs. 4.9 ng/ml, p<0.001) and in non-survivors (day 28 case fatality) compared to survivors (14.1 vs. 5.1 ng/ml, p<0.001). A high PTX3 level predicted the need for ICU stay (p<0.001) and hypotension (p<0.001). AUCROC in the prediction of severe sepsis was 0.73 (95% CI 0.66–0.81, p<0.001) and 0.69 in case fatality (95% CI 0.58–0.79, p<0.001). PTX3 at a cut-off level for 14.1 ng/ml (optimal cut-off value for severe sepsis) showed 63% sensitivity and 80% specificity. At a cut-off level 7.7 ng/ml (optimal cut-off value for case fatality) showed 70% sensitivity and 63% specificity in predicting case fatality on day 28.In multivariate models, high PTX3 remained an independent predictor of severe sepsis and case fatality after adjusting for potential confounders.ConclusionsA high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection.

Abstract 9934: Levels of Plasma Pentraxin 3 Predict Presence of Thin-cap Fibroatheroma in Patients with Stable Angina Pectoris: Assessment by Optical Coherence Tomography

Background: Thin-cap fibroatheroma (TCFA) is the primary type of rupture prone plaque, but biomarkers predicting it are not established. Recently, pentraxin 3 (PTX3) has been shown to be a novel biomarker specific to vascular inflammation. The aim of this study was to clarify the association between plasma PTX3 level and TCFA as determined by optical coherence tomography (OCT) in patients with stable angina pectoris (SAP). Methods: Thirty-four patients with SAP who underwent OCT at de novo culprit lesions before percutaneous coronary intervention were evaluated. TCFA was defined as a plaque with lipid contents in &gt;90°and with thinnest part of the fibrous cap measuring &lt;70μ m. Plasma PTX3 and serum high sensitive C-reactive protein (hsCRP) were measured among these patients. Plasma PTX3 level was categorized into low (&lt; 25th percentile), intermediate (25th to 75th percentiles), and high (&gt; 75th percentile) groups. Results: Fourteen patients with TCFA and 20 patients without TCFA were identified. Levels of PTX3 (median [interquartile range]) were significantly greater in patients with TCFA than without TCFA (4.66 [2.44 - 6.80]) vs. 2.60 [1.79 - 3.18] ng/mL; p = 0.009). Levels of hsCRP were comparable between the two groups. PTX3 level significantly inversely correlated with fibrous cap thickness (r = -0.53, p = 0.009), but hsCRP did not. The frequency of TCFA was 22, 29, and 88% in low, intermediate, and high PTX3 group, respectively (p = 0.009). Univariate analysis revealed that hypercholesterolemia, statin use, and level of PTX3 were related to the presence of TCFA. Multivariate logistic regression analysis in these factors showed that plasma PTX3 level was the significant independent factor associated with TCFA existence (OR, 1.99; 95%CI, 1.10 - 3.58; p = 0.023). The area under the receiver-operating characteristics curve for PTX3 level for prediction of TCFA was 0.766 (p = 0.009). The optimal cut-off value of PTX3 for predicting TCFA was 2.88 ng/mL (sensitivity 71%, specificity 70%). Conclusions: Plasma PTX3 level was associated with the presence of TCFA and thinner fibrous cap thickness at coronary culprit lesions in patients with SAP. These findings suggest that plasma PTX3 might be a useful marker reflecting the plaque vulnerability.

Plasma Pentraxin 3 is Associated with Cardiovascular Disease in Hemodialysis Patients

This cross-sectional study evaluates the associations of Pentraxin 3 (PTX3) and cardiovascular disease (CVD) in hemodialysis (HD) patients. Plasma was obtained from 98 maintenance HD patients before and after a session of HD and 50 age-matched healthy subjects. We measured plasma PTX3 levels by enzyme-linked immunosorbent assay. Our results showed that plasma PTX3 levels were significantly higher in HD patients compared with controls (1.87 vs. 1.11 ng/mL, p < 0.001), and increased acutely after a single HD session (post-HD 2.18 ng/mL vs. pre-HD 1.87 ng/mL, p < 0.001). Patients with CVD had higher plasma PTX3 levels than those without CVD (2.18 vs. 1.76 ng/mL, p < 0.05). Plasma PTX3 levels correlated positively with cardiac troponin T (ρ = 0.287, p = 0.007) and carotid artery intima-media thickness (ρ = 0.294, p = 0.043). High plasma PTX3 (>1.87 ng/mL) level was positively and independently associated with CVD (OR = 3.15, p = 0.024). Receiver operator characteristics analysis showed the correlation between PTX3 and CVD more closely than high sensitivity C-reactive protein (hs-CRP) in patients whose hs-CRP were higher than 3 mg/L. The area under the curve for PTX3 and hs-CRP was 0.655 (p = 0.047) and 0.562 (p = 0.458), respectively. Moreover, plasma PTX3 levels correlated negatively with body mass index, hemoglobin, pre-albumin, total cholesterol, triglyceride, and low-density lipoprotein. These data support the main conclusions: PTX3 levels are markedly elevated in HD patients; HD procedure itself induces PTX3 elevation; plasma PTX3 is associated with CVD in maintenance HD patients.

High pentraxin-3 plasma levels associate with thrombocytopenia in acute Puumala hantavirus-induced nephropathia epidemica

Our aim was to investigate whether plasma levels of the long pentraxin-3 (PTX3) associate with the severity of Puumala hantavirus-induced nephropathia epidemica (NE). Sixty-one prospectively identified consecutively hospitalized NE patients were examined. Plasma PTX3, interleukin (IL)-6, terminal complement complex SC5b-9, complement component C3, C-reactive protein (CRP), creatinine, sodium, kynurenine, and tryptophan levels, as well as the blood cell count, were determined for up to five consecutive days after hospitalization. Receiver operating characteristic (ROC) analysis revealed that the maximum PTX3 level >101.6 ng/ml (high PTX3) showed a sensitivity of 71% and a specificity of 89% for detecting platelet level <50 × 10(9)/l, with an area under the curve (AUC) value of 0.78 (95% confidence interval [CI] 0.63-0.94). High PTX3 level was also associated with several other variables reflecting the severity of the disease: patients with high PTX3 level had higher maximum blood leukocyte (16.1 vs. 9.7 × 10(9)/l, p < 0.001), plasma IL-6 (16.9 vs. 9.0 pg/ml, p = 0.007), and creatinine (282 vs. 124 μmol/l, p = 0.007) levels than patients with low maximum PTX3 level. They also had longer hospital stays (8 vs. 5 days, p = 0.015) compared to patients with low PTX3 level. High plasma PTX3 levels are associated with thrombocytopenia and the overall severity of NE.

Serum fetuin-A and pentraxin 3, status in hemodialysise and renal transplant patients

Systemic inflammation contributes to obesity-associated complications. The short pentraxin C-reactive protein (CRP) is a validated inflammatory marker, whereas long pentraxin-3 (PTX3) limits inflammation and is adaptively stimulated by proinflammatory cytokines in vitro. Severely obese (SO) patients (body mass index [BMI]>40] have the highest obesity-associated complications and increasingly undergo surgical treatment. SO-associated changes in plasma PTX3 and their interactions with systemic inflammation are, however, unknown.We sought to determine potential alterations in plasma PTX3 and their associations with changes in inflammatory markers before and after weight loss induced by laparoscopic Roux-en-Y gastric bypass (LRYGB).University hospital in Trieste, Italy.Plasma PTX3, CRP, and cytokines, including tumor necrosis factor α and interleukin 6 were measured in (1) 24 individuals with severe, class III obesity (SO; age = 42±1 yr, female/male = 18/6, BMI = 45±1 kg/m2) before and 3, 6, and 12 months after LRYGB; and (2) age- and sex-matched normal-weight (N; n = 56, BMI = 22±.2 kg/m2) or class I obese individuals (O; n = 44, BMI = 31.2±.3 kg/m2).SO, but not O, had higher plasma PTX3 compared with N, associated with highest proinflammatory cytokines and CRP (P<.05 versus N-O). In all patients, plasma interleukin 6 and tumor necrosis factor α were associated positively with PTX3 (P<.05). Plasma CRP and proinflammatory cytokines declined during LRYGB-induced weight loss. In contrast, high PTX3 further increased and remained elevated (P<.05 versus basal).Obesity level and energy balance modulate interactions between PTX3 and systemic inflammation. Elevated PTX3 is a novel, potentially adaptive alteration associated with proinflammatory cytokines in SO. Their differential changes conversely suggest circulating PTX3 as a novel negative inflammatory marker in SO undergoing LRYGB-induced weight loss.

The association of long pentraxin 3 on prognosis in pancreatic carcinoma patients on gemcitabine-based chemotherapy.

10536 Background: Advanced pancreatic carcinoma (PC) has a poor prognosis, nevertheless, gemcitabine and FOLFILINOX have been established as the standard chemotherapy. We previously reported that C-reactive protein (CRP) is one of the prognostic markers in advanced PC. CRP, serum amyloid P component and long pentraxin 3 (PTX3) belong to the pentraxin family of pattern recognition molecules involved in acute-phase response and innate immunity. Inflammatory mediators present in the tumor milieu may promote cancer progression and are considered promising targets for novel biological therapeutic approaches. Methods: We used PC cell lines (MIA Paca-2, AsPC-1, BxPC-3 and PANC-1) to validate the expression of PTX3 levels (Perseus Proteomics Inc.) using an enzyme-linked immunosorbent assay (ELISA) and examined cell biology with a migration and invasion assay. Moreover, we have prospectively assigned chemotherapy naïve advanced PC patients to estimate the relation between the clinical manifestation and the plasma PTX3 levels. Survival analysis and statistical testing for independent prognostic factors were performed using log-rank tests and Cox regression. Results: In vitro, we could show that MIA Paca-2 and PANC-1 highly express PTX3. High levels of expression of PTX3 in PC cells are associated with promoting paracrine PTX3 from the monocyte cell line (THP-1). Moreover, PC cells overexpressing PTX3 promote migration and invasion. In advanced PC patients (n = 70), and the mean PTX3 level at baseline was 5.23 ± 3.84 ng/mL (range: 0.9-17.7 ng/mL). In this population, 17 out of 70 patients were defined as having high PTX3 expression (cut off, 5.2 ng/mL). The median overall survival times were 265 days in PTX3low and 112 days in PTX3high (Log-rank: p = 0.001). The median progression free survival times were 109 days in PTX3low and 80 days in PTX3high (Log-rank: p = 0.27). A Cox multivariate analysis showed that high PTX3 levels were associated with the mortality risk. Conclusions: PTX3 as a clinical biomarker is one of the prognostic factors for advanced PC and can be considered as a promising target of novel biological therapy for PC.

High Plasma Level of Long Pentraxin 3 (PTX3) Is Associated with Fatal Disease in Bacteremic Patients: A Prospective Cohort Study

IntroductionLong pentraxin 3 (PTX3) is an acute-phase protein secreted by various cells, including leukocytes and endothelial cells. Like C-reactive protein (CRP), it belongs to the pentraxin superfamily. Recent studies indicate that high levels of PTX3 may be associated with mortality in sepsis. The prognostic value of plasma PTX3 in bacteremic patients is unknown.MethodsPlasma PTX3 levels were measured in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococcae and Escherichia coli, using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA). Values were measured on days 1–4 after positive blood culture, on day 13–18 and on recovery.ResultsThe maximum PTX3 values on days 1–4 were markedly higher in nonsurvivors compared to survivors (44.8 vs 6.4 ng/ml, p<0.001) and the AUCROC in the prediction of case fatality was 0.82 (95% CI 0.73–0.91). PTX3 at a cut-off level of 15 ng/ml showed 72% sensitivity and 81% specificity for fatal disease. High PTX3 (>15 ng/ml) was associated with hypotension (MAP <70 mmHg)(OR 7.9;95% CI 3.3–19.0) and high SOFA score (≥4)(OR 13.2; 95% CI 4.9–35.4). The CRP level (maximum value on days 1 to 4) did not predict case fatality at any cut-off level in the ROC curve (p = 0.132). High PTX3 (>15 ng/ml) remained an independent risk factor for case fatality in a logistic regression model adjusted for potential confounders.ConclusionsPTX3 proved to be a specific independent prognostic biomarker in bacteremia. PTX3 during the first days after diagnosis showed better prognostic value as compared to CRP, a widely used biomarker in clinical settings. PTX3 measurement offers a novel opportunity for the prognostic stratification of bacteremia patients.

A New Prognostic-Predictor Marker of Cardiovascular Disease for Obstructive Sleep Apnea: Pentraxin 3

Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent complete or partial upper airway obstruction during sleep causing hypoxia, sleep disruption, daytime sleepiness, mental and physical effects is the second most common respiratory condition; affecting 0.3- 4% of the middle- aged population (1). OSAS is strongly associated with cardiovascular morbidity and mortality, including an increased risk of endothelial dysfunction and atherosclerosis (2). The increased prevalence of hypertension and atherogenesis among OSAS patients has been attributed to sympathetic activation and endothelial dysfunction, likely resulting from initiation and propagation of inflammatory responses within the microvasculature (3). There is increasing evidence that OSAS associated with inflammatory cytokines and markers such as C-reactive protein (CRP), interleukin-6, fibrinogen, tumor necrosis factor alpha which are closely-involved in atherosclerosis, plaque formation and rupture (4). OSAS, a potent activator of inflammation, inreases CRP which has been used as an inflammatory biomarker for prediction of cardiovascular events;CRP is named as classical short pentraxins and is a acute phase protein produced from the liver in response to inflammatory mediators (5). Pentraxin 3 (PTX3), a new defined member of the pentraxin family, is produced from the major cell types involved in atherosclerotic lesions, including vascular endothelial-smooth muscle cells, macrophages, and neutrophils in response to inflammatory stimuli, however CRP is produced only from liver (6,7). Furthermore, CRP represents a systemic response to local inflammation, whereas PTX3 is rapidly produced directly from damaged tissues and directly reflects only the inflammatory state of the vasculature. The last but not the least PTX3 levels have been reported to be significantly elevated in acute myocardial infarction (7). In the light of these knowledge, PTX3 is able to reflect ACS condition better than CRP, it is highly possible that PTX3 is a superior biomarker to predict future cardiovascular events. Therefore, we speculate that OSAS, directly or indirectly, induces a persisting systemic and vascular inflammation and may cause PTX3 secretion. Since high PTX3 level is a sign of vascular inflammation which is the trigger point for many diseases that may occur secondary to OSAS, might also be a good marker of cardiovascular disease in OSAS. Screening of PTX3 level in OSAS patients may be a useful marker for evaluating the prognosis of OSAS. To address this hypothesis, further prospective studies are warranted to evaluate the role of PTX3 in patients with OSAS.

Plasma Pentraxin 3, but not High-sensitivity C-reactive Protein, is a Useful Inflammatory Biomarker for Predicting Cognitive Impairment in Elderly Hypertensive Patients

Due to the increasing longevity of human populations worldwide, there is need of a useful biomarker for the early detection of cognitive impairment in elderly persons. Both high blood pressure (BP) and inflammatory processes have been reported to be involved in cognitive impairment via cerebrovascular atherosclerosis or neuronal cell damage. In this cross-sectional study of 210 ambulatory elderly hypertensive patients without clinically evident dementia (mean age: 74 years; 44% men), we measured 24-hour BP, circulatory pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) levels, and cognitive function (Mini-Mental State Examination [MMSE]). A high plasma PTX3 level was observed in lean subjects, especially in those whose current body weight was lower than that measured 5 years earlier, whereas a high hs-CRP level was associated with obesity (all p < .05). Both PTX3 and hs-CRP levels were significantly associated with the MMSE score (r = -.248, p<0.001 and r = -.153, p<0.05, respectively); however, in multiple regression analysis, the PTX3 level, but not the hs-CRP level, was inversely associated with the MMSE score independently of patient demographics, glucose and lipid metabolic parameters, 24-hour systolic BP (SBP) level, and the atherosclerotic burden (all p < .05). Moreover, there was a significant interaction between the PTX3 and 24-hour SBP levels in the determinants of MMSE score (p < .05). A high plasma PTX3 level in elderly hypertensive patients, particularly in those with a high 24-hour BP level, could be a significant predictor of cognitive impairment. A high PTX3 level may be a marker of frailty in elderly hypertensive patients.