Pentraxin 3 Levels Research Articles

Plasma Pentraxin 3 is a More Potent Predictor of Endothelial Dysfunction than High-Sensitive C-Reactive Protein

An inflammatory response is a key event for endothelial dysfunction. Pentraxin 3 (PTX3) is an inflammatory protein produced at inflammation sites such as leukocytes and vascular endothelial cells. Here, we compared the relationships between endothelial function assessed by flow-mediated dilation (FMD), and the levels of plasma PTX3 and high-sensitive C-reactive protein (hsCRP), another inflammatory protein of the pentraxin family. Levels of FMD, PTX3 and hsCRP were measured twice within 6 to 8 months and retrospectively analyzed in 36 patients with coronary artery disease. We examined the associations between the values of FMD and the levels of PTX3 and hsCRP at the first measurement, and between the change ratios (second value/first value) of these parameters. Univariate linear regression analysis showed significantly negative correlations between FMD values and PTX3 and hsCRP levels at the first measurement, and significant associations with taking statins or calcium antagonists. Multivariate linear stepwise regression analysis identified PTX3 levels and taking statins and calcium antagonists as independent factors for endothelial function. The change ratio of FMD correlated more closely with that of PTX3 than of hsCRP (r = -0.446, P = 0.006 versus r = -0.330, P = 0.050). Significantly more patients with decreased FMD values had increased levels of PTX3 than those of hsCRP at the second measurement compared with the fi rst measurement. Furthermore, the ratio of patients with increased PTX3, but not increased hsCRP, was significantly reduced among those with increased, rather than decreased, FMD values. Endothelial dysfunction might be more accurately predicted by plasma PTX3 levels than by serum hsCRP levels.

Serum amyloid A, fetuin-A, and pentraxin-3 levels in patients with ischemic stroke: novel prognostic biomarkers?

Inflammation plays an important role in acute ischemic stroke. In this study we aimed to investigate the relationship between acute ischemic stroke and serum amyloid A, fetuin-A, and pentraxin-3 which are inflammation markers. We enrolled 52 patients with acute ischemic stroke and 30 sex-matched control subjects in the study. The patients were followed for 3 months. We evaluated the common risk factors, laboratory variables, and neurological examination of stroke patients according to prognosis scales. The median serum amyloid A, fetuin-A, and pentraxin-3 levels in the stroke patients were higher than in control subjects (respectively, P = 0.000, P = 0.002, and P = 0.037). National Institutes of Health Stroke Scale scores, glucose, C-reactive protein, fibrinogen, and white blood cell count showed differences within the group in terms of the serum amyloid A tertiles statistically. Pentraxin-3, fetuin-A, and serum amyloid A all arise together as novel prognostic factors in a group of patients with ischemic stroke. Relationships between higher levels of inflammation markers, especially serum amyloid A, and the severity of acute ischemic stroke were shown.

Prognostic value of plasma pentraxin-3 levels in patients with stable coronary artery disease after drug-eluting stent implantation.

Pentraxin-3 (PTX3) is an inflammatory marker thought to be more specific to cardiovascular inflammation than C-reactive protein (CRP). Our aim was to assess the prognostic value of PTX3 in patients with stable coronary artery disease (CAD) after drug eluting stent (DES) implantation. Plasma PTX3 levels were measured before percutaneous coronary intervention (PCI) and at 24 h post-PCI in 596 consecutive patients with stable CAD. Patients were followed up for a median of 3 years (range 1–5) for major adverse cardiovascular events (MACEs). We found that the post-PCI plasma PTX3 levels were significantly higher at 24 h after PCI than pre-PCI, patients with MACEs had higher post-PCI PTX3 levels compared with MACEs-free patients, patients with higher post-PCI PTX3 levels (median > 4.384 ng/mL) had a higher risk for MACEs than those with PTX3 < 4.384 ng/mL, and post-PCI PTX3, cTnI, multiple stents, and age but not high-sensitivity CRP (hsCRP) were independently associated with the prevalence of MACEs after DES implantation. The present study shows that post-PCI PTX3 may be a more reliable inflammatory predictor of long-term MACEs in patients with stable CAD undergoing DES implantation than CRP. Measurement of post-PCI PTX3 levels could provide a rationale for risk stratification of patients with stable CAD after DES implantation.

Pentraxin 3 as a Prognostic Biomarker in Patients with Systemic Inflammation or Infection

Purpose. The long pentraxin 3 (PTX3) is a key component of the humoral arm of the innate immune system. PTX3 is produced locally in response to proinflammatory stimuli. We reviewed the usefulness of systemic levels of PTX3 in critically ill patients with systemic inflammatory response syndrome (SIRS), sepsis, and bacteremia, focusing on its diagnostic and prognostic value. Methods. A PubMed search on PTX3 was conducted. The list of papers was narrowed to original studies of critically ill patients. Eleven papers on original studies of critically ill patients that report on PTX3 in SIRS, sepsis, or bacteremia were identified. Results. Systematic levels of PTX3 have little diagnostic value in critically ill patients with SIRS, sepsis, or bacteremia. Systemic levels of PTX3, however, have superior prognostic power over other commonly used biological markers in these patients. Systemic levels of PTX3 correlate positively with markers of organ dysfunction and severity-of-disease classification system scores. Finally, systemic levels of PTX3 remain elevated in the acute phase and decreased on recovery. Notably, the age of the patients and underlying disease affect systemic levels of PTX3. Conclusions. The diagnostic value of PTX3 is low in patients with sepsis. Systemic levels of PTX3 have prognostic value and may add to prognostication of patients with SIRS or sepsis, complementing severity-of-disease classification systems and other biological markers.

The time profile of Pentraxin 3 in patients with acute ST-elevation myocardial infarction and stable angina pectoris undergoing percutaneous coronary intervention.

Background. High levels of Pentraxin 3 (PTX3) are reported in acute myocardial infarction (AMI). Aim. To investigate circulating levels and gene expression of PTX3 in patients with AMI and stable angina pectoris (AP) undergoing PCI. Methods. Ten patients with AP and 20 patients with AMI were included. Blood samples were drawn before PCI in the AP group and after 3 and 12 hours and days 1, 3, 5, 7, and 14 in both groups. Results. Circulating PTX3 levels were higher in AMI compared to AP at 3 and 12 hours (P < 0.001 and P = 0.003). Within the AMI group, reduction from 3 hours to all later time points was observed (all P ≤ 0.001). Within the AP group, increase from baseline to 3 hours (P = 0.022), followed by reductions thereafter (all P < 0.05), was observed. PTX3 mRNA increased in the AMI group from 3 hours to days 7 and 14 in a relative manner of 62% and 73%, while a relative reduction from baseline to 3 and 12 hours of 29% and 37% was seen in the AP group. Conclusion. High circulating PTX3 levels shortly after PCI in AMI indicate that AMI itself influences PTX3 levels. PTX3 mRNA might be in response to fluctuations in circulating levels.

Annual decline in pentraxin 3 is a risk of vascular access troubles in hemodialysis patients.

Pentraxin 3 (PTX3), a multifunctional modulator of the innate immunoinflammatory response, is higher in patients undergoing hemodialysis than healthy control. Our study focused on annual change in PTX3 levels in patients with chronic hemodialysis, because regularly undergoing hemodialysis for many years modifies vascular inflammatory status. To demonstrate whether annual change in PTX3 is associated with vascular events, we measured blood levels of pentraxins (PTX3 and high-sensitivity C-reactive protein (hsCRP)) at baseline and in the next year in 76 hemodialysis patients and observed 20 patients with vascular access troubles during follow-up years. The annual decline in PTX3, but not hsCRP, is a significant risk of the incidence of vascular access trouble that is a critical and specific complication for hemodialysis patients (hazard ratio; 0.732 per +1 ng/mL/year in PTX3, * P = 0.039). This study is the first to focus on the annual change of pentraxins in a hemodialysis cohort.

Reciprocal Action of Pentraxin-3 and CRP in Women with Polycystic Ovary Syndrome

The aim of this study was to investigate the relationship between pentraxin-3 and other biochemical parameters in women with polycystic ovary syndrome (PCOS). We compared 58 women with PCOS to 34 body mass index- and age-matched normally menstruating healthy controls. Women with PCOS had significantly higher DHEA-S, free testosterone, LH and FAI, but lower pentraxin-3 levels when compared to healthy controls (0.86±0.21 and 0.91±0.14 respectively, p=0.014). Levels of CRP and lipoprotein-a were higher in the PCOS group. Overweight PCOS had significantly higher insulin, HOMA-IR, FAI, free testosterone and CRP and statistically significantly lower HDL and SHBG levels when compared to controls. Pentraxin-3 levels of obese and normal weight PCOS were similar. CRP and pentraxin-3 might contribute reciprocally to metabolic events and chronic low-grade inflammation in women with PCOS.

Pentraxin 3 Is Highly Specific for Predicting Anatomical Complexity of Coronary Artery Stenosis as Determined by the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery Score.

Background and ObjectivesThe aim of this study was to examine the hypothesis that pentraxin 3 (PTX3) can have a diagnostic value for predicting anatomical complexity of coronary artery stenosis as measured by the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score.Subjects and MethodsWe investigated the association of systemic arterial PTX3 with SYNTAX score among 500 patients with ischemic heart disease assigned to medical treatment (251), percutaneous coronary intervention (PCI) (197), or coronary artery bypass graft (CABG) (52).ResultsThe clinical judgment of the cardiologists was near-perfectly concordant with the SYNTAX score. Mean {99% confidence intervals (CIs)} SYNTAX scores were 5.8 (5.1-6.6), 18.4 (17.1-19.8), and 33.2 (32.8-33.6) in patients assigned to medical therapy, PCI, and CABG, respectively. The AROC (95% CIs) for discriminating between patients with and without a high SYNTAX score (>23) was 0.920 (0.895-0.946) for systemic arterial levels of PTX3. As the systemic arterial level of PTX3 increased, the SYNTAX scores also increased almost in a curvilinear fashion, with the value corresponding to the SYNTAX score of 23 being 0.29 ng · dL-1. This cutpoint achieved a sensitivity of 0.66 (0.57-0.74), a specificity of 0.94 (0.91-0.96), a positive predictive value of 0.79 (0.70-0.87), and a negative predictive value of 0.89 (0.85-0.92).ConclusionWe observed that systemic arterial levels of PTX3 were associated with the SYNTAX score in a curvilinear fashion. The discriminatory power of systemic arterial levels of PTX3 for a high SYNTAX score was excellent. The interesting finding of this study was the near perfect concordance between the decisions made by the cardiologists based on their clinical judgment and the SYNTAX score. The systemic arterial PTX3 level of 0.29 ng · dL-1 was highly specific for diagnosing complex coronary artery stenosis.

Relationships of Elevated Systemic Pentraxin-3 Levels With High-Risk Coronary Plaque Components and Impaired Myocardial Perfusion After Percutaneous Coronary Intervention in Patients With ST-Elevation Acute Myocardial Infarction

We aimed to assess the relationships of pentraxin-3 (PTX3) with coronary plaque components and myocardial perfusion after percutaneous coronary intervention (PCI) in order to clarify the mechanisms underlying the prognostic function of PTX3 in ST-elevation acute myocardial infarction (STEMI) patients. We enrolled 75 STEMI patients who underwent pre-PCI virtual histology (VH)-intravascular ultrasound. Relationships of the systemic pre-PCI PTX3 level with coronary plaque components and post-PCI myocardial blush grade (MBG) were evaluated. Lesions with elevated pre-PCI PTX3 (median ≥3.79ng/ml) had higher frequencies of VH-derived thin-cap fibroatheroma (65.8% vs. 24.3%, P<0.0001), plaque rupture (63.2% vs. 24.3%, P=0.001), and post-PCI MBG (0-1) (65.8% vs. 40.5%, P=0.03) than those with PTX3 <3.79ng/ml. In multivariate analysis, pre-PCI PTX3 level was independently related to post-PCI MBG (0-1) (odds ratio, 11.385; 95% confidence interval (CI), 1.346-96.289; P=0.026). At 9-month follow-up, cardiac event-free survival was poorer for patients with post-PCI MBG (0-1) (log-rank test χ(2)=8.6; P=0.003). Cox proportional-hazards analysis showed post-PCI MBG (0-1) (hazard ratio, 4.109; 95% CI, 1.372-12.309; P=0.012) and Killip class >2 on admission (hazard ratio, 5.356; 95% CI, 1.409-20.359; P=0.014) as independent predictors of adverse cardiac events during follow-up. Systemic pre-PCI PTX3 was associated with high-risk plaque components and impaired post-PCI myocardial perfusion. Thus, PTX3 may be a reliable predictor of outcome in STEMI patients.

The Acute-Phase Protein PTX3 is an Essential Mediator of Glial Scar Formation and Resolution of Brain Edema after Ischemic Injury

Acute-phase proteins (APPs) are key effectors of the immune response and are routinely used as biomarkers in cerebrovascular diseases, but their role during brain inflammation remains largely unknown. Elevated circulating levels of the acute-phase protein pentraxin-3 (PTX3) are associated with worse outcome in stroke patients. Here we show that PTX3 is expressed in neurons and glia in response to cerebral ischemia, and that the proinflammatory cytokine interleukin-1 (IL-1) is a key driver of PTX3 expression in the brain after experimental stroke. Gene deletion of PTX3 had no significant effects on acute ischemic brain injury. In contrast, the absence of PTX3 strongly compromised blood-brain barrier integrity and resolution of brain edema during recovery after ischemic injury. Compromised resolution of brain edema in PTX3-deficient mice was associated with impaired glial scar formation and alterations in scar-associated extracellular matrix production. Our results suggest that PTX3 expression induced by proinflammatory signals after ischemic brain injury is a critical effector of edema resolution and glial scar formation. This highlights the potential role for inflammatory molecules in brain recovery after injury and identifies APPs, in particular PTX3, as important targets in ischemic stroke and possibly other brain inflammatory disorders.

Plasma levels of pentraxin-3, an inflammatory protein involved in fertility, are reduced in women with polycystic ovary syndrome

Pentraxin-3 (PTX3), like C-reactive protein (CRP), is an acute-phase protein that belongs to the pentraxin superfamily. Moreover, it is expressed in the cumulus oophorus and appears to be involved in female fertility. The aim of the present study was to assess whether PTX3 levels are altered in polycystic ovary syndrome (PCOS) women and whether they show any relationship with the main features of these subjects. A cross-sectional study was conducted at the outpatient clinic of an academic centre. A total of 66 women affected with PCOS and 51 healthy controls were studied. Plasma PTX3 and serum CRP were measured by ELISA. Androgens were measured by liquid chromatography-mass spectrometry and free testosterone was measured by equilibrium dialysis. In PCOS women, insulin sensitivity was assessed by the glucose clamp technique. Adjusting for age and BMI, plasma PTX3 was reduced in PCOS women (P=0.036), in contrast with serum CRP, which was increased (P=0.004). In multiple regression analysis, serum androgens and other endocrine and ovarian features of PCOS were predictors of PTX3 levels, whereas body fat was the main independent predictor of CRP concentrations. Plasma PTX3 levels were reduced in PCOS women and independently associated with hyperandrogenism and other endocrine and ovarian features of PCOS.

Plasma PTX3 levels in sickle cell disease patients, during vaso occlusion and acute chest syndrome (data from Saudi population)

BackgroundSickle cell disease (SCD) is a chronic, incurable hereditary disease. The vaso-occlusive crisis (VOC) is the most frequently occurring acute complication in sickle cell patients and accounts for the majority of SCD-related hospital admissions. Another major complication is the potentially fatal acute chest syndrome (ACS). The prototypic long pentraxin-3 (PTX3), an acute phase protein and a key component of innate immunity, is linked to ischemia-induced inflammation, a condition incriminated in SCD complications.AimTo investigate the expression of PTX3 in stable SCD and VOC patients and to assess its relation to the development and progression of ACS.Subjects and methodsWe conducted this study on 160 patients with confirmed SCD (20 stable SCD and 140 in VOC), and 10 healthy age- and sex-matched controls. Patients were diagnosed as SCD by high-performance liquid chromatography. PTX3 levels were assessed using enzyme-linked immunosorbant assay.ResultsIn the stable state, all 20 SCD patients had PTX3 levels (range = 0.9–2.1 ng/ml; median = 1.1) comparable to those of healthy controls (range = 0.8–2.0 ng/ml; median = 1.0) (P > 0.05). During the VOC, plasma PTX3 significantly increased (range = 8.7–37.2 ng/ml; median = 22.3) (P < 0.01). Out of 140 VOC patients, 15 (10.7%) developed ACS and four required mechanical ventilation, of which two died. The median plasma level of PTX3 (22.3 ng/ml) was set as a cut-off value to stratify patients into low- and high-PTX3 expressers. Of the 140 VOC patients, 43 (30.7%) had PTX3 levels >22.3 ng/ml, of these, 13 patients developed ACS (13/43; 30.2%); of the remaining 97 patients who had PTX3 ≤22.3 ng/ml, only two patients (2/97; 2.1%) progressed to ACS, with a further increment in PTX3 in all of them. PTX3 levels were correlated with length of hospital stay in VOC patients and markers of lung injury in ACS patients.ConclusionPTX3 levels were higher in SCD patients in VOC, being associated with longer hospital stay. Higher initial PTX3 concentrations were related to the development of ACS with a further increase in PTX3 levels observed upon progression to ACS. Thus, PTX3 could be used as a subjective method to predict occurrence and severity of SCD acute complications.

Pentraxin 3 is associated with disease activity but not atherosclerosis in patients with systemic lupus erythematosus

Objectives Pentraxin 3 (PTX3) plays an important role in inflammation, immunity, and atherosclerosis. Plasma PTX3 level has drawn attention as a marker that responds to local inflammation. Systemic lupus erythematosus (SLE), a chronic inflammatory disorder which can affect multiple organs, develops atherosclerosis prematurely. We examined the hypotheses that the concentration of plasma PTX3 increases in patients with SLE and that PTX3 is associated with the disease activity and premature atherosclerosis.Methods Plasma PTX3 concentrations were measured in 65 patients with SLE and 53 control subjects. The patients were also evaluated with respect to their clinical characteristics, disease activity indices, and corticosteroid therapy. We performed carotid ultrasonography to measure subclinical atherosclerosis in patients with SLE.Results Plasma PTX3 concentration of the SLE patients was significantly higher than that of the healthy controls (median 3.9 vs. 2.0 ng/mL, p < 0.001). In patients with SLE, PTX3 concentrations were correlated with SLEDAI (p = 0.011), BILAG index (p < 0.001), C-reactive protein (p < 0.001), anemia (p = 0.020), hypoalbuminemia (p = 0.022), and daily dose of prednisolone (p = 0.008) after adjustment for age and sex. PTX3 was not associated with disease duration, anti-ds DNA antibody, CH50, or carotid atherosclerosis.Conclusions Patients with SLE have increased concentrations of PTX3 compared with control subjects. PTX3 was significantly associated with disease activity but not with carotid atherosclerosis.

Echocardiography, Spirometry, and Systemic Acute-Phase Inflammatory Proteins in Smokers with COPD or CHF: An Observational Study

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP), pentraxin 3 (PTX3), interleukin-1β (IL-1 β), and soluble type II receptor of IL-1 (sIL-1RII) were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged ≥50 years and with ≥10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 β, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects). Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 β, and sIL-1RII compared with CHF patients and control subjects (p < 0.05). None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation.

Long pentraxin PTX3 attenuates ischemia reperfusion injury in a cardiac transplantation model

Ischemia reperfusion (IR) injury is a major issue in cardiac transplantation, and inflammatory processes play a major role in myocardial IR injury. Long pentraxin-3 (PTX3) is a member of a phylogenetically conserved group of acute-phase reactants that are involved in inflammation and innate immunity. In our study, hearts of C57Bl/6 mice were flushed and stored in cold Bretschneider solution for 8 h and then transplanted into syngeneic recipient. We found that both mRNA and protein levels of PTX3 were increased following myocardial IR injury; neutralizing antibody against PTX3 aggravated cardiomyocyte apoptosis and recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24 h after myocardial IR injury was reduced by exogenous PTX3 administration and increased by PTX3 neutralization in comparison with control. Cardiac output at 60 mmHg of afterload pressure was also increased in hearts with exogenous PTX3 administration and decreased with PTX3 neutralization (PTX3: 58.4 ± 7.4 ml/min; 24.5 ± 3.8 ml/min; Anti-PTX3: 11.6 ± 1.7 ml/min; P < 0.05). Furthermore, PTX3 restricted expansion of γδ T cell that was the major source of IL-17A and down-regulated expression of IL-23 and IL-17A. In conclusion, PTX3 played a protective role in cardiomyocyte IR injury. PTX3 ameliorated cardiomyocyte apoptosis and infiltration of neutrophil and macrophage and then improved hemodynamic performance. This was associated with restricted γδ T-cell expansion and decreased IL-23/IL-17A expression.

Cardiorespiratory fitness does not alter plasma pentraxin 3 and cortisol reactivity to acute psychological stress and exercise

Pentraxin 3 (PTX3) has been recently identified as a biomarker of vascular inflammation in predicting cardiovascular events. The purpose of this study was to examine the effect of cardiorespiratory fitness on plasma PTX3 and cortisol responses to stress, utilizing a dual-stress model. Fourteen male subjects were classified into high-fit (HF) and low-fit (LF) groups and completed 2 counterbalanced experimental conditions. The exercise-alone condition (EAC) consisted of cycling at 60% maximal oxygen uptake for 37 min, while the dual-stress condition (DSC) included 20 min of a mental stress while cycling for 37 min. Plasma PTX3 revealed significant increases over time with a significant elevation at 37 min in both HF and LF groups in response to EAC and DSC. No difference in plasma PTX3 levels was observed between EAC and DSC. In addition, plasma cortisol revealed a significant condition by time interaction with greater levels during DSC at 37 min, whereas cardiorespiratory fitness level did not reveal different plasma cortisol responses in either the EAC or DSC. Aerobic exercise induces plasma PTX3 release, while additional acute mental stress, in a dual-stress condition, does not exacerbate or further modulate the PTX3 response. Furthermore, cardiorespiratory fitness may not affect the stress reactivity of plasma PTX3 to physical and combined physical and psychological stressors. Finally, the exacerbated cortisol responses to combined stress may provide the potential link to biological pathways that explain changes in physiological homeostasis that may be associated with an increase in the risk of cardiovascular disease.

Pentraxin-3 Serum Levels Are Associated with Disease Severity and Mortality in Patients with Systemic Inflammatory Response Syndrome

The long pentraxin-3 (PTX3) is a key component of the humoral arm of the innate immune system. PTX3 is produced locally in response to pro-inflammatory stimuli. To investigate PTX3 levels and its use as a biomarker in patients with systemic inflammation, we developed a solid-phase enzyme-linked immunosorbent assay based on novel anti-PTX3 monoclonal antibodies detecting PTX3 with high sensitivity. The assay was applied on 261 consecutive patients admitted to an intensive care unit prospectively monitored with the systemic inflammatory response syndrome (SIRS). 100 blood donors were included as controls. PTX3 levels were elevated in patients (median = 71.3 ng/ml) compared with the controls (median = 0 ng/ml) (Mann-Whitney, p<0.0001). ROC analysis showed that PTX3 levels were significantly specific (85.0%) and sensitive (89.1%) to discriminate between healthy controls and patients (area under the curve (AUC) 0.922 (95% CI 0.892 to 0.946, p<0.0001)). Higher levels of PTX3 were associated with the development of sepsis, severe sepsis and septic shock (p = 0.0001). The serum levels of PTX3 correlated significantly with SAPS2 score (Spearman's rho 0.28, p<0.0001). Patients with high levels of PTX3 at admission did have a higher 90 day mortality rate than patients with the 25% lowest levels (Cox regression analysis, hazard ratio 3.0, p = 0.0009). In conclusion, we have established a highly sensitive and robust assay for measurement of PTX3 and found that its serum concentrations correlated with disease severity and mortality in patients with SIRS and sepsis.

Plasma long pentraxin 3 as a marker of endothelial dysfunction in early diabetic nephropathy

Abstract Objective This study investigated the utility of measuring plasma long pentraxin 3 (PTX3) levels in the early detection of endothelial dysfunction compared with Von Willebrand factor (vWF) activity and flow-dependent arterial dilatation (well-known markers of endothelial dysfunction) in early diabetic nephropathy. Materials and methods A total of 50 Egyptian patients with type 2 diabetes and 20 healthy controls were recruited from the Diabetes, Endocrinology and Metabolism center, Faculty of Medicine, Cairo University. The diabetic patients were divided into two equal groups of comparable age and sex: group I consisted of patients with normal urinary albumin excretion and group II consisted of patients with microalbuminuria. Results In group II, the plasma PTX3 level was significantly higher (median value 2.3 ng/ml) and the mean flow-mediated dilatation (FMD; 0.433 ±0.059) was significantly lower when compared with the control group (PTX3 1.15 ng/ml, FMD 0.901 ± 0.04; P&lt;00001) and with group I (PTX3 1.2 ng/ml, FMD 0.627± 0.05; P&lt;0.0001). The vWF activity (median value) was significantly higher in the two diabetic groups compared with controls (20.2, 16.3 and 4% in group I, group II, and controls, respectively; P&lt;0.0001), with no significant difference between the two diabetic groups. There was a significant positive correlation between PTX3 levels and vWF activity (P&lt;0.001), diabetes duration, and concentration of fasting blood sugar, HbA1c, cholesterol, and triglyceride and a significant negative correlation between PTX3 levels and FMD (P&lt;0.001) in all diabetic patients. In group II, there was a significant positive correlation between PTX3 levels and vWF activity (r= 0.603, P= 0.001). Conclusion PTX3 may represent a useful endothelial dysfunction marker in early diabetes nephropathy.

148. Acute bipolar disorder depression is associated with immune activation

Recent studies indicate that immune activation may be an important component of the pathogenesis of bipolar disorder. The study sample consists of 40 patients admitted to the hospital with a diagnosis of acute bipolar depression. Blood samples were drawn at 3 time points: at time of hospital admission, during the acute hospital stay, and at a six month follow-up. Inflammatory markers were measured including C-reactive protein (CRP), Pentraxin 3 (PTX3), and antibodies to infectious agents. The markers in the bipolar depressed patients were studied over the 3 time points and also compared to those in other groups: 60 hospitalized for acute mania; 69 with recent onset psychosis; 246 with multi-episode schizophrenia; 98 with bipolar disorder not selected for mania or depression; and 222 non-psychiatric controls. The bipolar depressed patients had elevated levels of CRP at all 3 time points. The bipolar depressed patients also had elevated levels of PTX3 at hospital admission which were reduced during the hospital stay and at follow-up. The bipolar depressed group also had elevated levels of antibodies to the nucleocapsid protein of the SARS strain of coronavirus, while elevated levels of these antibodies were not found in the other groups. Our study indicates that bipolar disorder depression is associated with immune activation, particularly during acute exacerbations. These findings may lead to the development of new methods of prevention and treatment.

Pentraxin 3 is a local inflammatory marker in atrial fibrillation

Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local inflammatory lesions while C-reactive protein (CRP) is produced mainly in the liver. In this study, we investigated whether a local level of PTX3 might be a sensitive marker for the local inflammation of AF. Blood from the periphery and left atrial appendage (LAA) was sampled from 23 patients with AF undergoing pulmonary vein isolation, and from 10 control subjects with Wolff-Parkinson-White syndrome. We measured peripheral and LAA plasma concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and PTX3. Plasma PTX3 concentrations in both locations were higher in patients with AF than in control subjects. PTX3 concentrations were significantly higher in the LAA than the periphery in patients with AF (3.7 ± 1.4 vs 3.3 ± 1.2 ng/ml, P < 0.01), but not in control subjects (2.4 ± 0.5 vs 2.4 ± 0.5 ng/ml, not significant). Patients and controls showed no significant differences in CRP, IL-6, or TNF-α concentrations between the periphery and LAA. Interestingly, there was a significant positive correlation between LAA plasma concentrations of PTX3 and left atrial volume (r = 0.55, P < 0.01). These data demonstrate that local PTX3 production in the left atrium might reflect the local inflammation of AF.