Pentraxin 3 Levels Research Articles

Effects Of Aerobic Training On Pentraxin 3/Toll-like Receptor 4 And Oxidative Status In Elderly Adults

PURPOSE: The consequence of reactive oxygen and nitrogen species (ROS/RNS)-mediated cellular aging has been linked to various diseases, such as atherothrombosis and cancer. One of the possible mechanisms for these ROS-mediated diseases is through the activation of intracellular pattern recognition receptors (PRR), thereby contributing to a chronic low-grade pro-inflammatory systemic state in aging. Pentraxin 3 (PTX3) is a soluble PRR mainly released from endothelial cells and immunes cells and utilizes its counter-regulatory function in promoting the anti-inflammatory response via the inhibition of toll-like receptor 4 (TLR4). Although increased level of PTX3 has been shown following stimulation of oxidative stress and is also associated with aging-related diseases, the relationship between PTX3 and oxidative stress in aging remains to be elucidated. However, exercise has been proposed as the key intervention for the maintenance of health in the elderly. Therefore, this study was to examine whether or not the level of PTX3 on TLR4-dependent inflammation would be associated with changes in oxidative stress in both plasma and peripheral blood mononuclear cells (PBMCs) following 8 weeks of aerobic training in the elderly. METHODS: Fourteen elderly subjects (9 trained and 5 controls) were recruited to participate in an 8-week aerobic training. The ELISA and western blot analyses were used to determine the levels of PTX3 and biomarkers of oxidative stress in both plasma and PBMCs prior to and following training. RESULTS: No changes in plasma levels of PTX3 and oxidative stress markers (GSH, TEAC, and ROS/RNS) were observed in trained vs. control groups. However, our analyses showed a downregulation of PTX3 expression in PBMCs (P = 0.017) following aerobic training, along with decreased ratio of PTX3/TLR4 (P = 0.047). Furthermore, the tendency of oxidative stress response in PBMCs remained unchanged as shown in plasma levels. Finally, no correlation was observed between PTX3 and any oxidative stress biomarkers following training protocol. CONCLUSIONS: These findings demonstrate the downregulation of PTX3 and PTX3/TLR4 ratio in PBMCs of elderly subjects, irrespective of changes in oxidative stress following 8 weeks of aerobic training.

Pentraxin-3 mediates prosurvival actions of interferon tau in bovine luteinized granulosa cells.

Pentraxin 3 (PTX3), a multimeric glycoprotein, is implicated in various biological functions. PTX3 was shown to be elevated in the corpus luteum (CL) of early pregnant ewes; however, its role in sheep or other ruminants' CL during this reproductive stage or how it is regulated remain unknown. Here we explored the role of PTX3 and its relationship with interferon-tau (IFNT; the pregnancy recognition signaling molecule during early pregnancy in domestic ruminants) in bovine luteinized granulosa cells (LGCs). IFNT robustly elevated PTX3 expression in bovine LGCs, and significantly stimulated its expression in luteal endothelial cells, along with CL slices; yet, LGCs were the most responsive and sensitive among these luteal models. ALK2/ALK3/ALK6 kinase inhibitor, dorsomorphin, dose-dependently inhibited basal and IFNT-elevated PTX3 expression in LGCs. In contrast, ALK4/5/7 inhibitor, SB431542, did not alter basal and TGFB1-induced PTX3. We found that recombinant human PTX3 itself moderately but significantly increases LGC numbers. Because PTX3 is highly expressed in bovine LGCs, we next examined the impact of lowering endogenous PTX3 levels with siRNA. PTX3 silencing decreased the viable cell numbers and reversed IFNT actions on cell viability, percentage of proliferating cells, and on two key survival/death genes: BIRC5 encoding surviving protein, and FASL - a death-inducing signal. Interestingly, thrombospondin-1, a known luteal proapoptotic factor, was inversely related to PTX3 in LGCs. Together, these findings suggest a novel role for PTX3 during early pregnancy, as mediator of IFNT prosurvival actions supporting CL maintenance during this reproductive stage.

Association between pentraxin-3 and the risk of preeclampsia: A meta-analysis.

An association between circulating pentraxin-3 (PTX3) and the risk of preeclampsia (PE) remains to be established. We performed a meta-analysis of observational studies to evaluate their relationship.The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and WanFang databases were searched for related observational studies evaluating PTX3 and PE risk. A random-effects or a fixed-effects model was used in the meta-analysis, depending on the heterogeneity among the included studies.Nine case–control studies were included, with 396 PE patients and 438 controls. The results showed that PTX3 was significantly higher in pregnant women with PE as compared to those without PE (standardized mean difference [SMD] = 2.48, P < .001), with significant heterogeneity (I2 = 98%), particularly for those over 30 years old (SMD = 3.75, P < .001). Subsequent analyses showed that patients with severe or early-onset PE had higher PTX3 levels compared to those with mild or late-onset PE (SMD = 0.93, P = .01), suggesting that PTX3 may be a marker of PE severity. The association between PTX3 and PE was not significantly affected by the statistical method used. Sensitivity analyses by omitting one study at a time did not significantly affect the results. However, the funnel plots were asymmetric, suggesting the potential existence of publication bias.PTX3 may be related to the risk and severity of PE in pregnant women. These results should be evaluated and confirmed in cohort studies.

Effects of Methylene Blue on Ovarian Torsion-Detorsion Injury in a Rat Model.

Methylene blue (MB) is an antioxidant that ameliorates ischemia-reperfusion injury in several tissues. We analyzed the effects of MB as an inhibitor of torsion-detorsion injury in rat ovaries. Rats were randomly divided into 5 groups. Group 1 was the sham group, in which only laparotomy was performed. Group 2 was the torsion group, with 3hours of ischemia. Group 3 was the torsion+MB group, with 3hours of ischemia after MB administration. Group 4 was the torsion-detorsion group, with 3hours of ischemia and reperfusion. Finally, group 5 was the torsion-detorsion+MB group, with 3hours of ischemia and MB administration before detorsion/reperfusion. Ovary injuries were histopathologically scored. Malondialdehyde (MDA) and total protein levels in ovarian tissues were determined, and long pentraxin-3 (PTX3) levels were measured in ovarian tissue using an enzyme-linked immunosorbent assay. In comparing group 4 with group 5 and group 2 with 3, histopathological parameters reflecting injury were significantly increased in groups 4 and 2. Group 3 generated increased MDA levels when compared with group 2 (P<.05). However, there was no significant difference between groups 2 and 3 in terms of plasma PTX3 levels. MDA and PTX3 levels decreased in group 5 in comparison with group 4 for MDA (P<.000) and PTX3 levels (P<.01). MB alleviated ischemia-reperfusion ovary injury in our experimental model.

Elevated Levels of Pentraxin 3 Correlate With Neutrophilia and Coronary Artery Dilation During Acute Kawasaki Disease.

Kawasaki disease (KD) is the leading cause of acquired pediatric heart disease in the developed world as 25–30% of untreated patients and at least 5% of treated patients will develop irreversible coronary artery lesions (CAL). Pentraxin-3 (PTX-3) has been well-studied in inflammatory diseases, particularly in cardiovascular diseases associated with vascular endothelial dysfunction. We hypothesized that PTX-3 plays an important role in the development of KD-associated CAL and investigated the circulating levels of PTX-3 in the serum of KD patients. Children with acute KD were followed from diagnosis through normalization of the clinical parameters of inflammation (convalescent phase). Serum samples were obtained and echocardiograms were conducted at several phases of the illness: acute [prior to intravenous immunoglobulin (IVIG) treatment], sub-acute (5–10 days after IVIG treatment), and convalescent (1–4 months after KD diagnosis). Seventy children were included in the final cohort of the study, of whom 26 (37%) presented with CAL and 18 (26%) developed IVIG resistance. The patients included in this study came from diverse ethnic backgrounds, mostly with mixed ancestry/ ethnicity. Significantly increased PTX-3 levels were observed during the acute phase of KD compared to the sub-acute and the convalescent phases. The PTX-3 levels during acute KD were significantly higher among KD patients with CAL compared to patients with normal coronary arteries (NCA). Also, the PTX-3 levels were significantly higher in patients with IVIG resistance. Furthermore, the PTX-3 levels were significantly higher in IVIG-resistant KD patients with CAL as compared to the NCA group. Moreover, the PTX-3 levels were significantly correlated to coronary artery z-score during acute KD and to neutrophil counts throughout KD progression regardless of coronary artery z-score. Elevated PTX-3 levels correlated to elevated neutrophil counts, a known source of PTX-3 in acute inflammation and an important player in the development of KD vasculitis. We, therefore, suggest PTX-3 as a novel factor in the development of KD-associated CAL and propose neutrophil-derived PTX-3 as contributing to KD vascular dysfunction.

Pentraxin 3 (PTX-3) Levels in Bronchoalveolar Lavage Fluid as a Lung Cancer Biomarker.

In this study, we investigated the utility of pentraxin 3 (PTX-3) in bronchoalveolar lavage fluid (BALF) as lung cancer (LCa) diagnostic. A total of 89 LCa patients and 84 non-LCa patients who received bronchoscopy in the First Affiliated Hospital of Xi'an Jiaotong University from December 2014 to February 2015 were enrolled. LCa was subdivided according to pathological type (scale, gland, and small cell lung cancer). BALF samples were obtained during bronchoscopy and PTX-3 levels assayed by ELISA. t-tests, Mann-Whitney, and Kruskal-Wallis tests were performed for the comparison of PTX-3 levels between the different groups. Correlation analysis and receiver operating characteristic (ROC) analysis were used to analyze clinical data. The levels of PTX-3 increased in the LCa groups. PTX-3 levels were higher in the small cell lung cancer (SCLC) compared to non-small-cell lung cancer (NSCLC) groups. In LCa patients, obstructive pneumonia could upregulate the expression of PTX-3 in BALF. The area under the ROC curve of PTX-3 in BALF during LCa diagnosis, SCLC, and LCa with obstructive pneumonia was 0.949 (p ≤ 0.001), 0.672 (p < 0.05), and 0.838 (p < 0.01), respectively. In conclusion, PTX-3 in BALF has a potential value as an LCa biomarker, particularly in cases of SCLC and LCa with obstructive pneumonia.

AB0051 SERUM AMYLOID A AND PENTRAXIN 3: INNATE IMMUNE RESPONSE AND DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS

Background:Systemic Lupus Erythematosus (SLE) is an autoimmune disease that involves several molecular patterns with a wide spectrum of clinical manifestations and symptoms. Inflammation and related pathway play a role in SLE pathogenesis. The pentraxin superfamily including long and short pentraxin, C Reactive Protein CRP, Serum amyloid A (SAA), Pentraxin 3 (PTX3) are key components of innate immune system and induce a variety of inflammation associated pathway. However Literature provides several evidences that CRP serum levels not correlated with clinical and immunological manifestations. This situation affected clinical practice and the patient follow up. PTX3 have been identified as a component of inflammatory status in several autoimmune conditions. SAA is an acute phase protein secreted in large quantity during inflammation.Objectives:We want to evaluated SAA, PTX3 and CRP concentrations, their correlation between SLE Disease Activity Index (SLEDAI), that including complement fractions C3, C4.Methods:We enrolled fifty patients that fulfilled the SLE American College of Rheumatology criteria and fifty healthy subjects. The SLE disease activity was classified with the SLEDAI (0 to 12). Patients were divided into two groups according to SLEDAI score: inactive group (Group 1, 25 patients, 50%: SLEDAI &lt; 4) and active group (Group 2, 25 patients, 50%: SLEDAI 5 to 12). PTX3 concentration was measured by a sandwich ELISA kit (Hycult) with 2.8 ng/mL cut-off point. SAA concentration was detected by nephelometry performed on a BN ProSpec System (Siemens, Germany), with assay kit based on polyclonal antibodies (Siemens Healthcare Diagnostics Products, Germany, 6.5 mg/L cut-off point). High sensitive CRP concentrations were determined using the ci8200 platform (Abbott Laboratories Chicago, Illinois).Results:Plasma PTX3 and serum SAA levels was significantly higher in SLE patients than in the healthy subjects (PTX311.5 ± 7.3 ng/mL vs 2.3 ± 1.1; p &lt; 0.001; SAA: 87 ±77 mg/L vs 2.6±2.5; p &lt; 0.001). These differences were not evident in CRP levels (8.5 ± 7.8 mg/L vs 6.2± 2.5). Considering two groups, there were statistical differences in PTX3 level (Group 2: 14.9 ± 12 ng/mL vs Group 1: 2.16 ±0.5 ng/mL, p&lt;0,05) and SAA concentration (Group 2: 114 ± 89 ng/mL vs Group 1: 3.6 ±1.7 ng/mL, p&lt;0,05) but not in CRP concentration (Group 2: 11.5 ± 8.4 mg/L vs Group 1: 9.5 ±3.5). There was a significantly negative correlation between C3, C4 fractions, PTX3 and SSA levels (respectively r = −0.74, p=&lt;0.05, and r = −0.79, p&lt;0.05). No statistical correlation were appeared between C3, C4 fractions and CRP serum levels (r= −0,12., p= 0.82, and r= −0.18, p= 0,21). We noted a positive significant correlation between SLEDAI, PTX3 and SAA concentration (r = 0.79, p &lt; 0.05, 0.83, p &lt; 0.05, respectively) an increase in PTX3 and SAA levels followed the lupus flare and symptoms. No significant correlation appeared between SLEDAI and CRP (r= 0.15, p=0.89)Conclusion:PTX3 and SAA concentration was significantly higher in SLE patients than the healthy control subjects and their levels reflected disease activity. We showed a direct correlation between PTX3 and SAA. In SLE patients PTX3 and SAA concentrations were correlated with SLEDAI. We suggest an integrate viewpoint in witch SAA and PTX3 may play a role as a biomarker of disease activity, with synergic work during SLE events. Evidences suggested that PTX3 and SAA could trigger the same molecular pathway, by TLR4, via NF-kB.

P0936INJURY OF NEUTROPHILS DURING HAEMODIALYSIS AND ITS INVOLVEMENT FOR DEVELOPMENT OF CHRONIC MICROINFLAMMATION

Abstract Background and Aims Owing to the quality developments of membrane material and dislysis water, it is believed that the biocompatibility of haemodialysis (HD) system has been considerably improved. However, mortality and morbidities of dialysis patients have remained unacceptably high, which raises a question as to the biocompatibility improvement of current HD systems. Method Seventy-one patients on regular HD (male/female: 52/19, mean age: 63 years old, median HD duration: 19 months, HD session 3 times a week for 3 to 4 hours each by using high performance synthetic membrane) at Tohoku University Hospital were examined. Blood samples were obtained from all patients before and after the HD session, to measure followings; number of white blood cell fraction, and apotosis cells, plasma levels of following molecules; myeloperoxidase (MPO), pentraxin 3, angiogenin, lactoferrin, complement (C3a, C5a, C5b-9), and 17 cytokines. Apoptosis (positive for Annexin-V-FITC and negative for propidium iodide) was measured in 100,000 cells by flow cytometer, and plasma molecules were measured by ELISA kit. Results The main findings of this study were as follows (changes in the values after HD as compared to the pre HD); the significant decrease of leukocytes counts (neutrophil and lymphocyte), significant increases of apoptosis positive cells of leukocytes (neutrophiles and monocytes), significant increases of plasma MPO and pentraxin3 levels, significant decrease of angiogenin, and, no or only marginal changes in plasma pro-inflammatory cytokine levels and complement products. There was a significant positive correlation between the change in MPO and apoptosis before and after HD. Conclusion Bio-incompatibility of HD has remained a crucial issue even in the current systems. Among the several pathologies, process of neutrophile apoptosis accompanying MPO degranulation, may plays a central role for developing microinflammation. In this regard, change of plasma MPO could be a clinical marker for the biocompatibility of HD system. And in order to achieve better patients’ outcomes, innovative HD systems which fully improve biocompatibility are needed.

P1058COMPARISON OF THE REMOVAL EFFICIENCY AND THE BIOCOPATIBILITY BETWEEN PRE- AND POST-DILUTION ON-LINE HEMODIAFILTRATION

Abstract Background and Aims On-line HDF (OL-HDF) performed in Japan is characterized by the fact that pre-dilution OL-HDF (pre-HDF) accounts for 95% of the cases. In Europe, post-dilution OL-HDF (post-HDF) is the mainstream mode, and particularly high-volume post-HDF is reportedly associated with a favorable prognosis in patients. Last year, we reported favorable biocompatibility and removal efficiency of low-volume post-HDF using high-performance hemodiafilters. Here, we performed pre-HDF and post-HDF for 4 weeks each under the same conditions in the previous study and compared the removal efficiency and the biocompatibility. Method Nine stable dialysis patients who had received pre-HDF for at least 6 months (age, 60.8±15.4 years; dry weight, 54.5±9.5 kg) were included in this study. Fineflux-210 Seco (asymmetric triacetate membrane, NIPRO) was used as a hemodiafilter. Post-HDF (replacement fluid rate, 12 L/session) was performed in the first session and pre-HDF (replacement fluid rate, 60 L/session) in the second, each lasting 4 weeks. Each study parameter was evaluated on the last day of each session. In either session, HDF was performed at a blood flow rate of 250 mL/min and a total dialysate flow rate of 500 mL/min. Each HDF cycle lasted 4 h. The removal efficiency was evaluated in terms of Kt/V, as well as the removal rates and removal volumes of urea, creatinine, β2-microglobulin (MG), and α1-MG. Biocompatibility was evaluated in terms of the rates of changes in the levels of CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), pentraxin-3 (PTX3), and intercellular adhesion molecule-1 (ICAM-1) before and after dialysis. Changes in the levels of CD62P during dialysis were also examined. Paired t-test was used for statistical analysis. Results Removal efficiency results: The removal efficiency for small molecular weight solutes was significantly higher in post-HDF. The removal rate (%) and removal volume (g/session) of β2-MG were 81.4±3.6 and 0.224±0.051 in post-HDF and 80.7±3.3 and 0.218±0.029 in pre-HDF, respectively. The removal rate (%) and removal volume (g/session) of α1-MG were 37.0±4.0 and 0.151±0.024 in post-HDF and 33.3±4.1 and 0.133±0.026 in pre-HDF, respectively. The amount of albumin leakage (g/session) was 3.7±0.6 in post-HDF and 3.1±0.7 in pre-HDF, indicating a significant difference. Biocompatibility results: There were no significant differences between the two modes in the rates of changes in the levels of CRP, PTX3, IL-6, TNF-α, or ICAM-1 before and after treatment. The rate of expression of CD62P was also not significantly different. Conclusion Under the present conditions using high-performance filters, post-HDF and pre-HDF demonstrated favorable removal efficiency for both small and large molecular weight solutes, and the biocompatibility was also favorable, indicating no significant differences between the two modes.

P1570INTERLEUKIN-6 (RS1800795) AND PENTRAXIN 3 (RS2305619) GENETIC POLYMORPHISMS AND THEIR RELATION WITH INFLAMMATION AND ALL-CAUSE MORTALITY IN ESRD PATIENTS ON DIALYSIS

Abstract Background and Aims Chronic inflammation plays an important role in progression and outcome of chronic kidney disease (CKD) patients. The interleukin-6 (IL-6) polymorphism, rs1800795, is a single nucleotide polymorphism (SNP) in the promoter region (-174G/C) that regulates gene transcription and affects the levels of this cytokine. Genetic variants in the promotor region have been associated with a poor outcome in several pathologies, namely in coronary artery disease. Pentraxin 3 (PTX3) is an inflammatory protein, produced locally by different cell types (e.g. mononuclear phagocytes, dendritic cells, fibroblasts and endothelial cells). PTX3 polymorphism, rs2305619, is a SNP (+281A&amp;gt;G) in the intron 1 of PTX3 gene. PTX3 polymorphisms have been described as risk factor for development of coronary artery disease and for an impairment of kidney function. Our aim was to determine the allelic frequencies of IL6 and PTX3 in end-stage renal disease (ESRD) patients and controls, as well as their relationship with the inflammatory response. Method We studied 289 ESRD patients on hemodialysis (high-flux hemodialysis or hemodiafiltration) and 22 healthy individuals, matched for gender, body mass index, and, as far as possible, for age. Real-Time PCR TaqMan SNP genotyping assays were used to assess allelic frequencies of IL6 (rs1800795) and PTX3 (rs2305619). We evaluated the circulating levels of PTX3, growth differentiation factor (GDF)-15, high-sensitivity C-reactive protein (hsCRP), IL-6, tumor necrosis factor-alpha (TNF-α), soluble TNF receptor 2 (sTNFR2), hepcidin and transferrin, using commercially available kits. Deaths occurring along 1-year follow-up period were recorded and mortality rates were evaluated for homozygous and heterozygous alleles. Results Compared to controls, all inflammatory biomarkers were significantly higher in ESRD patients. Allelic frequencies in ESRD patients and controls were similar for both SNPs, IL-6 -174G/C and PTX3 +281A&amp;gt;G, considering the homozygous and the heterozygous alleles. For the IL-6 -174G/C, the CC patients, compared to GG and heterozygous patients, showed significantly higher GDF-15 and CRP concentrations and significantly lower values of transferrin; moreover, we found that CC patients presented a trend towards higher mortality rate (21%, 10% and 7% for CC, GG and GC, respectively; P=0.072). For PTX3 +281A&amp;gt;G polymorphism, the AA patients, compared to GG and heterozygous patients, presented higher hsCRP; no significant differences were found in mortality rate between different allele carrier groups (P=0.703). Conclusion Although no differences were found in the allelic frequencies between controls and ERSD patients, the CC patients for IL6 polymorphism (rs1800795) and AA patients for PTX3 polymorphism (rs2305619), showed an enhanced inflammatory response; the association of the IL6 polymorphism with a higher mortality needs further studies.

PTX3 Predicts Myocardial Damage and Fibrosis in Duchenne Muscular Dystrophy.

Pentraxin 3 (PTX3) is a main component of the innate immune system by inducing complement pathway activation, acting as an inflammatory mediator, coordinating the functions of macrophages/dendritic cells and promoting apoptosis/necrosis. Additionally, it has been found in fibrotic regions co-localizing with collagen. In this work, we wanted to investigate the predictive role of PTX3 in myocardial damage and fibrosis of Duchenne muscular dystrophy (DMD). DMD is an X-linked recessive disease caused by mutations of the dystrophin gene that affects muscular functions and strength and accompanying dilated cardiomyopathy. Here, we expound the correlation of PTX3 cardiac expression with age and Toll-like receptors (TLRs)/interleukin-1 receptor (IL-1R)-MyD88 inflammatory markers and its modulation by the so-called alarmins IL-33, high-mobility group box 1 (HMGB1), and S100β. These findings suggest that cardiac levels of PTX3 might have prognostic value and potential in guiding therapy for DMD cardiomyopathy.

Pentraxin 3 in primary percutaneous coronary intervention for ST elevation myocardial infarction is associated with early irreversible myocardial damage

BackgroundThe inflammatory marker long pentraxin 3 (PTX3) has been shown to be a strong predictor of 30-day and one-year mortality after acute myocardial infarction. The aim of this study was to evaluate the kinetic profile of PTX3 and its relationship with interleukin 6 (IL-6), high-sensitive C-reactive protein (hs-CRP) and infarct size.MethodsPTX3, IL-6 and hs-CRP were measured at predefined time points, at baseline (before percutaneous coronary intervention (PCI)), at 12 and 72 hours after PCI in 161 patients with first-time ST elevation myocardial infarction (STEMI).ResultsPTX3 and IL-6 levels increased in the early phase, followed by a gradual decrease between 12 and 72 hours. There were statistically significant correlations between PTX3 and IL-6 in general, for all time points and for changes over time (0–72 hours). In a linear mixed model, PTX3 predicted IL-6 (p < 0.001). PTX3 is also correlated with hs-CRP in general, and at each time point post PCI, except at baseline. PTX3, IL-6 and hs-CRP were all significantly correlated with infarct size in general, and at the peak time point for maximum troponin I. In addition, there was a modest correlation between IL-6 levels at baseline and infarct size at 72 hours after PCI (ρ = 0.23, p = 0.006).ConclusionsPTX3 had a similar kinetic profile to IL-6, with an early increase and decline, and was statistically significantly correlated with markers of infarct size in STEMI patients post primary PCI. Baseline levels of IL-6 only predicted infarct size at 72 hours post PCI.

Oxidative Stress and Inflammatory Markers PTX3, CypA, and HB-EGF: How Are They Linked in Patients With STEMI?

We investigated circulating levels of inflammatory biomarkers pentraxin-3 (PTX3), cyclophilin A (CypA), and heparin-binding epidermal growth factor-like growth factor (HB-EGF); oxidative stress; and antioxidant status markers in the patients with ST-segment elevation acute myocardial infarction (STEMI) to better understand a relationship between inflammation and oxidative stress. We examined the impact of oxidative stress on high values of inflammatory parameters. The study included 87 patients with STEMI and 193 controls. We observed a positive correlation between PTX3 and HB-EGF (ρ = 0.24, P = .027), CyPA, and sulfhydryl (SH) groups (ρ = 0.25, P = .026), and a negative correlation between PTX3 and SH groups (ρ = -0.35, P = .001) in patients with STEMI. To better understand the effect of the examined parameters on the occurrence of high concentrations of inflammatory parameters, we grouped them using principal component analysis. This analysis identified the 4 most contributing factors. Optimal cutoff values for discrimination of patients with STEMI from controls were calculated for PTX3 and HB-EGF. An independent predictor for PTX3 above the cutoff value was a "metabolic-oxidative stress factor" comprised of glucose and oxidative stress marker prooxidant-antioxidant balance (odds ratio = 4.449, P = .030). The results show that higher PTX3 values will occur in patients having STEMI with greater metabolic and oxidative stress status values.

Determination of pentraxin 3 levels in diagnosis of appendicitis in children.

The aim of this study is to determine whether pentraxin 3 (PTX3) levels can be used in the diagnosis of appendicitis in children. Fifteen children under 18years old, who gave blood samples for reasons other than inflammatory conditions, and 40 children who were proved to have appendicitis (non-perforated or perforated) between August 2017 and January 2018, were enrolled in the study. Patients were classified into subgroups: group 1 (healthy children without any sign of inflammation, n=15), group 2 (non-perforated appendicitis, n=25), and group 3 (perforated appendicitis, n=15). The median PTX3 value was 1.01ng/mL (minimum value: 0.82, maximum: 1.28) in the control group. The median PTX3 values prior to surgery were 20.68ng/mL (minimum: 1.02, maximum: 28.471) and 1.46 (minimum: 1.05, maximum: 23.421) ng/mL for non-perforated appendicitis and perforated appendicitis respectively. The PTX3 levels were significantly higher in groups 2 and 3 than in group 1 (P<0.01). According to receiver operating characteristics analysis the cut-off value of PTX3 levels at admission for appendicitis was 1.30ng/mL with a sensitivity of 75% and a specificity of 100% (area under the curve, 0.939; P=0.000). Pentraxin 3 levels were significantly higher in children with appendicitis than in healthy children. Children with high PTX3 levels complaining of right lower quadrant pain may support a diagnosis of appendicitis. Future studies should be conducted to evaluate changes in PTX3 levels by comparing children with appendicitis versus acute abdominal pain in larger populations to further determine the value of PTX3 in the diagnosis of appendicitis in children.

Elevated levels of pentraxin 3 correlate with neutrophil counts and coronary artery dilation during acute Kawasaki disease, as a predictor of coronary artery lesions

Abstract Kawasaki disease (KD) is the leading cause of acquired heart disease in the developed world. 25–30% of untreated patients will develop irreversible coronary artery lesions (CAL). Pentraxin-3 (PTX-3), has been well studied in inflammatory diseases, in particular vascular endothelial dysfunction associated with cardiovascular disease. We hypothesized that PTX-3 played an important role in the development of KD associated CAL, and investigated circulating levels of PTX-3 in KD patients serum. Children with acute KD were followed from diagnosis through normalization of the clinical markers of inflammation. Blood draws and echocardiograms were conducted at several timepoints, acute (prior to IVIG treatment), sub-acute (5–10 days after IVIG treatment), and convalescent (1–4 months after KD diagnosis) phases. In this study we enrolled 70 children with KD, which included 26 (37%) who presented with CAL. Patients included in this study came from a diverse ethnic background. We observed a significant increase in PTX-3 levels during acute KD phase, compared to sub-acute and convalescent phases. PTX-3 levels during acute KD were significantly higher among KD patients with CAL. Further, PTX-3 levels were significantly correlated to coronary artery diameter size during acute KD and neutrophil counts throughout KD progression regardless of coronary artery diameter. We observed PTX-3 levels highly correlated to neutrophil counts, a known source of PTX-3 in acute inflammation and an important player in the development of KD vasculitis. Therefore, we propose PTX-3 as a novel factor associated with acute KD and in the development of KD associated CAL, and neutrophil derived PTX-3 as an important player of KD vascular dysfunction.

Elevated serum pentraxin 3 levels might predict the diagnosis of branch atheromatous disease at a very early stage.

Branch atheromatous disease (BAD) is one of the stroke subtypes caused by occlusion at the origin of a deep penetrating artery of the brain and is associated with a microatheroma or a junctional plaque. Patients with BAD often develop progressive worsening of neurologic deficits, although these patients often present minor stroke with clinical characteristics of lacunar syndrome at the onset. Pentraxin 3 (PTX3) is known to be a key molecule involved in the pathogenesis of atherosclerosis. Although a high level of serum PTX3 is observed in patients with acute coronary syndrome, there are no reports on PTX3 levels in patients with BAD. This study aimed to investigate whether serum PTX3 levels can distinguish BAD from other stroke subtypes. We investigated 93 patients with ischaemic stroke. Serum PTX3 levels on admission were measured using enzyme-linked immunosorbent assay in patients with BAD and those with other stroke subtypes (each n≥20). The median PTX3 levels in patients with BAD (4840pg/mL) were higher than those with other subtypes of stroke (3397pg/mL in lacunar stroke, 1298pg/mL in large-artery atherosclerosis, 1470pg/mL in cardioaortic embolism and 1006pg/mL in control) (all P<0.01). Our results suggest that elevated serum PTX3 levels might predict the diagnosis of BAD at a very early stage.

PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma.

Pentraxin-3 (PTX3) belongs to the pentraxine family, innate immune regulators involved in angiogenesis, proliferation and immune escape in cancer. Here, we evaluated PTX3 tissue expression and serum levels as biomarkers of clear cell renal cell carcinoma (ccRCC) and analyzed the possible role of complement system activation on tumor site. A 10-year retrospective cohort study including patients undergoing nephrectomy for ccRCC was also performed. PTX3 expression was elevated in both neoplastic renal cell lines and tissues, while it was absent in both normal renal proximal tubular cells (HK2) and normal renal tissues. Analysis of complement system activation on tumor tissues showed the co-expression of PTX3 with C1q, C3aR, C5R1 and CD59, but not with C5b-9 terminal complex. RCC patients showed higher serum PTX3 levels as compared to non-neoplastic patients (p<0.0001). Higher PTX3 serum levels were observed in patients with higher Fuhrman grade (p<0.01), lymph node (p<0.0001), and visceral metastases (p<0.001). Patients with higher PTX3 levels also showed significantly lower survival rates (p=0.002). Our results suggest that expression of PTX3 can affect the immunoflogosis in the ccRCC microenvironment, by activating the classical pathway of CS (C1q) and releasing pro-angiogenic factors (C3a, C5a). The up-regulation of CD59 also inhibits the complement-mediated cellular lysis.

Association of Pentraxin 3 rs2305619 (A/G) gene polymorphism and its serum level with the risk of nephropathy in type II diabetic patients

Diabetic nephropathy (DN) is one the microvascular diabetic complications. Pentraxin 3 (PTX3) belongs to the acute-phase reactants proteins and variation in the serum levels of PTX3 are accompanied with DN. This work was done on 180 subjects which included 3 groups: 60 patients of T2DM with nephropathy, 60 patients of T2DM without nephropathy and 60 age and sex matched healthy controls. Serum Pentraxin3 was measured by ELISA and Pentraxin 3 rs2305619 (A/G) variation was evaluated by using the TaqMan allelic discrimination assay. Resultsshowed a significant differences between the three groups regarding serum Pentraxin3 level and Pentraxin 3 rs2305619 (A/G) genotypes distribution with elevated serum Pentraxin3 level and increased GG genotype in patients with DN, increased AG genotype in patients without DN and elevated AA genotype in controls. GG genotypes of Pentraxin 3 rs2305619 (A/G) might be a risk factor for nephropathy in T2DM. ConclusionGG genotypes of Pentraxin3 rs2305619 gene polymorphism and high serum Pentraxin 3 level might be considered a genetic risk factor for nephropathy in T2DM.

Transforming growth factor-β1 suppress pentraxin-3 in human orbital fibroblasts.

Transforming growth factor-β (TGF-β), recognized as a crucial factor in regulating fibrosis and tissue remodeling, plays a role in thyroid-associated ophthalmopathy (TAO). Pentraxin-3 (PTX3), a member of pentraxins, was recently implicated in many autoimmune and fibrotic diseases. Thus, we hypothesize if there is a potential correlation between TGF-β and PTX3 in orbital fibroblasts (OFs). Several strains of OFs obtained from patients with TAO (n = 8) and healthy donors (n = 3) were established as the study model. Recombinant TGF-β1 was exerted as an intervention and the expression of PTX3 was detected. To uncover the underlying mechanism, specific inhibitors of TGF-β and siRNA knockdown of Smads were utilized. We found that TGF-β1 can reduce PTX3 protein expression in OFs. We also demonstrated that this downregulation was mediated at a pretranslational level, and PTX3 mRNA was inhibited in a time- and concentration-dependent manner by TGF-β1. Interestingly, the basic level of PTX3 and the magnitude of suppression were not significantly different between TAO and control groups. Furthermore, the TGF-β receptor complex (type I:type II) and the Smad2/3-Smad4-dependent pathway are essential for TGF-mediated PTX3 repression. These findings indicated that TGF-β1 can inhibit PTX3 expression in human OFs, which may participate in inflammation and fibrosis in patients with TAO and provide a potential target for the antifibrotic treatment.

Pentraxin-3 is a candidate biomarker on the spectrum of severity from pre-eclampsia to HELLP syndrome: GenPE study.

Pentraxin-3 has been reported as a promising biomarker of pre-eclampsia and its severity; however, available studies have small sample sizes, and analyses are not always adjusted for confounders. The aim of this study is to establish the strength of the association between maternal Pentraxin-3 level and pre-eclampsia or HELLP syndrome. It was a case-control study. Women with pre-eclampsia or HELLP syndrome were defined as cases, and women with healthy pregnancies at term (>37 weeks) were classified as controls. Plasma concentrations of Pentraxin-3 were determined at the time of delivery by quantitative enzyme immunoassay. Associations between Pentraxin-3 and pre-eclampsia and HELLP syndrome were assessed by multinomial logistic regression. Subsidiary analysis for the time of disease onset was also carried out. Odds ratios and 95% confidence intervals are reported. A total of 1024 pregnant women were included (461 controls, 368 pre-eclampsia, 195 HELLP). A positive log-linear relationship was found between the top pentraxin-3 quintile and HELLP syndrome. After adjustment for confounders (maternal age, ethnicity, socioeconomic position, date and place of recruitment, family history of pre-eclampsia, smoking, body mass index at beginning of pregnancy, gestational age and multiple pregnancy), the strength of the association was higher for HELLP syndrome [OR 1.13 (95% CI 1.08; 1.18)] than for pre-eclampsia [OR 1.03 (95% CI 1.03; 1.10)]. No difference according to time of onset or pentraxin-3 level was found. In summary, pentraxin-3 level was associated with pre-eclampsia, but it was more strongly associated with HELLP syndrome. Longitudinal studies with a lower probability of residual confounding are necessary to improve our knowledge about the role of pentraxin-3 in pre-eclampsia.