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Alberto Mantovani - One of the best experts on this subject based on the ideXlab platform.
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determination of Pentraxin 3 levels in cerebrospinal fluid during central nervous system infections
European Journal of Clinical Microbiology & Infectious Diseases, 2020Co-Authors: Marta Zatta, Alberto Mantovani, Barbara Bottazzi, Stefano Di Bella, Francesca Rossi, Pierlanfranco Dagaro, Ludovica Segat, Massimiliano Fabbiani, Roberto LuzzatiAbstract:Pentraxin 3 (PTX3) is an acute phase protein; its plasmatic levels significantly rise during severe infections. Data on PTX3 levels in cerebrospinal fluid (CSF) of patients with central nervous system (CNS) infections are lacking. We aimed (a) to assess the diagnostic potential of measuring CSF PTX3 levels in patients with CNS infections and (b) to establish CSF PTX3 cutoffs to distinguish between bacterial and aseptic meningoencephalitis (ROC curve). PTX3 levels were measured in CSF from 19 patients admitted to Trieste Hospital, Italy, with CNS infection. A diagnosis of bacterial infection and aseptic meningoencephalitis was made in 7 (37%) and 12 (63%) patients, respectively. Subjects with bacterial infections showed significantly higher PTX3 levels (13.5 vs 1.27 ng/mL in aseptic meningoencephalitis, p = 0.010). We identified two different CSF PTX3 levels cutoffs. (1) The best cutoff to maximise Youden’s J was 9.6 ng/mL with a sensitivity, specificity, positive predictive value and negative predictive value (NPV) of 71.4%, 91.4%, 83.3%, 84.6%, respectively. (2) The cutoff with higher NPV (100%) was 3.6 ng/mL; a diagnosis of bacterial infections was obtained in 0% patients with CSF PTX3 levels < 3.6 ng/mL vs 58% of those with CSF PTX3 levels ≥ 3.6 ng/mL (p = 0.017). CSF PTX3 levels are higher in bacterial meningitis than aseptic meningoencephalitis. A cutoff of 3.6 ng/mL of CSF PTX3 has a high NPV and can be used to exclude bacterial CNS infections.
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driver mutations jak2v617f mplw515l k or calr Pentraxin 3 and c reactive protein in essential thrombocythemia and polycythemia vera
Journal of Hematology & Oncology, 2017Co-Authors: Federico Lussana, Tiziano Barbui, Alessandro M Vannucchi, Alberto Mantovani, Alessandra Carobbio, Paola Guglielmelli, Silvia Salmoiraghi, Barbara Bottazzi, Roberto Leone, Alessandro RambaldiAbstract:Background The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs.
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role of Pentraxin 3 in shaping arthritogenic alphaviral disease from enhanced viral replication to immunomodulation
PLOS Pathogens, 2015Co-Authors: Suansin Foo, Cecilia Garlanda, Alberto Mantovani, Weiqiang Chen, Adam Taylor, Kuo Ching Sheng, Terk Shin Teng, Patrick C Reading, Helen Blanchard, Lara J HerreroAbstract:The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV) and Ross River virus (RRV), and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that Pentraxin 3 (PTX3) was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3-/-) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis.
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Pentraxin 3 ptx3 plasma levels and carotid intima media thickness progression in the general population
Nutrition Metabolism and Cardiovascular Diseases, 2014Co-Authors: Andrea Baragetti, Alberto Mantovani, Ivan Cuccovillo, Michael Knoflach, Stefan Kiechl, Liliana Grigore, Manuela Casula, K Garlaschelli, Georg Wick, Johann WilleitAbstract:Abstract Background and aim Pentraxin 3 (PTX3) is an essential component of the humoral arm of innate immunity and, like C-reactive protein, is independently associated with the risk of developing vascular events. Aim of this study was to investigate, in two large population-based surveys, the Bruneck Study and the PLIC Study, whether PTX3 plasma levels predict the progression of common carotid artery intima–media thickness (CCA-IMT), a surrogate marker of atherosclerosis, in the general population during 5 or 6 years of follow-up. Results In the Bruneck Study, PTX3 plasma levels did not predict a faster progression of CCA-IMT either in the carotid artery or in the femoral artery. This finding was confirmed in the PLIC Study where subjects within the highest tertile of PTX3 did not show an increased progression of CCA-IMT. PTX3 plasma levels were also not associated with the fastest maximum IMT progression. In summary, in more than 2400 subjects from the general population, PTX3 plasma level is neither an independent predictor of progression of subclinical atherosclerosis in different arterial territories, including carotid and femoral arteries nor of incident cardiovascular events. Conclusion These findings support the relevance of investigating the predictive value of PTX3 plasma levels only in specific settings, like overt CVD, heart failure or acute myocardial infarction.
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Pentraxin 3 in chronic heart failure the corona and gissi hf trials
European Journal of Heart Failure, 2012Co-Authors: Roberto Latini, Ivan Cuccovillo, Barbara Bottazzi, Thor Ueland, Lars Gullestad, Serge Masson, Stale H Nymo, Mari Vardal, Alberto MantovaniAbstract:Aims Pentraxin-3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF. Methods and results Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI-Heart Failure trial (GISSI-HF). The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors, high sensitivity C-reactive protein (hsCRP), and N-terminal pro brain natriuretic peptide (NT-proBNP). PTX3 concentration [median (Q1–Q3) = 5.34 (3.55–7.64) ng/mL, n = 2690] was higher in females, in older patients, and those with lower body mass index. Baseline elevated PTX3 was associated with a higher risk of all-cause mortality [759 events, hazard ratio (HR) for 1 SD increase 1.20, 95% confidence interval (CI) 1.12–1.30, P < 0.0001], cardiovascular mortality (587 events, HR 1.27, 95% CI 1.17–1.38, P < 0.0001), or hospitalization for worsening HF (720 events, HR 1.21, 95% CI 1.12–1.30, P < 0.0001), and marginally improved discrimination. Three-month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT-proBNP. Rosuvastatin lowered hsCRP levels but significantly raised PTX3. Conclusion In two independent clinical trials that enrolled patients with chronic HF, PTX3 was consistently associated with outcomes. The opposite effects of a statin on hsCRP and PTX3 call for further investigation. Trial registration NCT00336336 (GISSI-HF), NCT00206310 (CORONA).
Giuseppe Peri - One of the best experts on this subject based on the ideXlab platform.
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persisting high levels of plasma Pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality
Intensive Care Medicine, 2010Co-Authors: Tommaso Mauri, Giuseppe Peri, Ivan Cuccovillo, Andrea Coppadoro, Giacomo Bellani, Nicolò Patroniti, Massimo Cugno, Gaetano Iapichino, Luciano Gattinoni, Antonio PesentiAbstract:Purpose Pentraxin 3 (PTX3) is an inflammatory mediator produced by neutrophils, macrophages, myeloid dendritic and endothelial cells. During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur. PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis.
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Pentraxin 3 and c reactive protein in severe meningococcal disease
Shock, 2009Co-Authors: Tom Sprong, Giuseppe Peri, Alberto Mantovani, Chris Neeleman, Stefano Signorini, Jos W M Van Der Meer, Marcel Van DeurenAbstract:The long Pentraxin 3 (PTX3) is an important element of the innate immune system and has potential as a diagnostic tool in inflammatory conditions. We studied PTX3 in patients admitted to an intensive care unit with severe meningococcal disease and compared it with the short Pentraxin C-reactive protein (CRP). Twenty-six patients with meningococcal disease were studied, 17 patients presented with meningococcal septic shock (shock group), and 9 patients presented with meningococcal meningitis or bacteremia (no-shock group). Pentraxin 3 and CRP were measured by enzyme-linked immunosorbent assay. High plasma concentrations of PTX3 (median, 579 microg/L) were seen at admission in patients with meningococcal disease. Concentrations were significantly higher in patients with shock compared with patients without shock (medians, 801 and 256 microg/L, respectively; P = 0.006). In contrast, CRP at admission was lower in the shock group as compared with the no-shock group (medians, 58 and 165 mg/L, respectively; P = 0.008). High PTX3 and low CRP concentration at admission discriminated between presence and absence of shock (area under the receiver operating characteristic curve, 0.85; P = 0.007 for PTX3 and area under the receiver operating characteristic curve, 0.84; P = 0.01 for CRP). PTX3 did not correlate with disease severity (pediatric risk of mortality) and days spent in the intensive care unit. PTX3 at admission and PTX3 peak concentration both showed a negative correlation with plasma fibrinogen concentrations. C-reactive protein concentration at admission correlated negatively with disease severity. In conclusion, PTX3 was an early indicator of shock in patients with severe meningococcal disease that followed a pattern of induction distinct from CRP.
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Pentraxin 3 in acute respiratory distress syndrome an early marker of severity
Critical Care Medicine, 2008Co-Authors: Tommaso Mauri, Giuseppe Peri, Alberto Mantovani, Andrea Coppadoro, Giacomo Bellani, M Bombino, Nicolò Patroniti, Antonio PesentiAbstract:Objective: Pentraxin 3 is a fluid phase receptor involved in innate immunity. It belongs to the Pentraxins family, as C-reactive protein does. Pentraxin 3 is produced by a variety of tissue cells, whereas only the liver produces C-reactive protein. Pentraxin 3 plays a unique role in the regulation of inflammation. Acute lung injury and acute respiratory distress syndrome are characterized by an important inflammatory reaction. We investigated the role of Pentraxin 3 as a marker of severity and outcome predictor of acute lung injury and acute respiratory distress syndrome. Design: We measured circulating Pentraxin 3 and C-reactive protein levels within 24 hrs from intubation (day 1), after 24 hrs from the first sample, then every 3 days for the first month and then once a week, until discharge from the intensive care unit. Pentraxin 3 was also measured in bronchoalveolar lavages, performed when clinically indicated. Setting: One university medical center general intensive care unit. Patients: The study included 21 patients affected by acute lung injury and acute respiratory distress syndrome (1994 Consensus Conference criteria). Interventions: None. Measurements and Main Results: Pentraxin 3 plasma levels were high with a peak on the first day (median 71.05 ng/mL, interquartile range 52.37-117.38 ng/mL, normal values <2 ng/mL), declining thereafter. C-reactive protein peaked later and remained at relatively high values. Out of several day 1 parameters, Pentraxin 3 was the only significant difference between survivors and nonsurvivors. Pentraxin 3 levels were positively correlated with lung injury score values (p < 0.001) and number of organ failures (p < 0.001). Pentraxin 3 was present in bronchoalveolar lavages fluids (5.03 ng/mL, interquartile range 1.52-8.48 ng/mL) and bronchoalveolar lavages positive to bacterial culture were associated with significantly higher Pentraxin 3 values (p < 0.05). Conclusions: The results presented here show that Pentraxin 3 is elevated in acute lung injury and acute respiratory distress syndrome and that its levels correlate with parameters of lung injury and systemic involvement. The clinical and pathophysio-logical significance of Pentraxin 3 in acute lung injury and acute respiratory distress syndrome deserves further scrutiny.
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elevated plasma levels of the long Pentraxin Pentraxin 3 in severe dengue virus infections
Journal of Medical Virology, 2005Co-Authors: Albert T A Mairuhu, Giuseppe Peri, Tatty E Setiati, Erik C Hack, Penelopie Koraka, Augustinus Soemantri, Albert D M E Osterhaus, Dees P M Brandjes, Jos W M Van Der Meer, Alberto MantovaniAbstract:C-reactive protein is one of the most widely used indicators of the response of acute-phase proteins. The measurement of C-reactive protein in dengue, however, is clinically not useful, because of marginally elevated levels and absent association with disease severity. The prototypic long Pentraxin, Pentraxin 3, is an acute phase protein that is structurally related but distinct from C-reactive protein which has proven to correlate with the severity of bacterial infection in critically ill patients. The potential involvement of Pentraxin 3 in dengue and its aptitude to predict more severe disease or poor clinical outcome has not been studied previously. We therefore measured Pentraxin 3 plasma levels in 44 dengue virus infected patients. Pentraxin 3 levels were strikingly higher when compared to C-reactive protein levels, with highest Pentraxin 3 values observed in the first 7 days after the onset of symptoms. Median Pentraxin 3 levels at admission and peak levels during follow up were higher in patients suffering from dengue shock syndrome (at admission: 119.3 ng/ml [interquartile range 61.8--188.7], peak values during follow up: 147.9 ng/ml [interquartile range 85.7--204.3]) compared to levels found in patients with dengue fever and dengue hemorrhagic fever (at admission: 59.0 ng/ml [interquartile range 28.6--100.3], P=0.040; peak values during follow up: 80.8 ng/ml [interquartile range 36.1--168.1], P=0.020). Our results indicate that Pentraxin 3 seems to be a marker of infection better than C-reactive protein in dengue. The role of Pentraxin 3 in the pathogenesis of dengue and its potential as an early prognostic indicator of disease severity needs further assessment.
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ifn γ inducible protein 10 and Pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in mycobacterium tuberculosis infection
Microbes and Infection, 2005Co-Authors: Annalisa Azzurri, Giuseppe Peri, Alberto Mantovani, Oumou Sow, Amedeo Amedei, Boubacar Bah, Sadio Diallo, Marisa Benagiano, Mario Milco Delios, Gianfranco Del PreteAbstract:Abstract IFN-γ-inducible protein 10 (IP-10/CXCL10) is a chemokine involved in delayed-type hypersensitivity and attraction of monocytes and activated T lymphocytes at inflammatory foci, whereas Pentraxin 3 (PTX3) is part of the innate immune response. In the Republic of Guinea, 220 newly diagnosed, HIV-negative, pulmonary tuberculosis (TB) patients were studied together with 220 healthy household controls and 220 community controls. CXCL10 and PTX3 blood levels were assessed by ELISA at diagnosis, after 2 months and at the end of treatment. In untreated patients, both CXCL10 and PTX3 levels were higher ( P P P P
Barbara Bottazzi - One of the best experts on this subject based on the ideXlab platform.
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determination of Pentraxin 3 levels in cerebrospinal fluid during central nervous system infections
European Journal of Clinical Microbiology & Infectious Diseases, 2020Co-Authors: Marta Zatta, Alberto Mantovani, Barbara Bottazzi, Stefano Di Bella, Francesca Rossi, Pierlanfranco Dagaro, Ludovica Segat, Massimiliano Fabbiani, Roberto LuzzatiAbstract:Pentraxin 3 (PTX3) is an acute phase protein; its plasmatic levels significantly rise during severe infections. Data on PTX3 levels in cerebrospinal fluid (CSF) of patients with central nervous system (CNS) infections are lacking. We aimed (a) to assess the diagnostic potential of measuring CSF PTX3 levels in patients with CNS infections and (b) to establish CSF PTX3 cutoffs to distinguish between bacterial and aseptic meningoencephalitis (ROC curve). PTX3 levels were measured in CSF from 19 patients admitted to Trieste Hospital, Italy, with CNS infection. A diagnosis of bacterial infection and aseptic meningoencephalitis was made in 7 (37%) and 12 (63%) patients, respectively. Subjects with bacterial infections showed significantly higher PTX3 levels (13.5 vs 1.27 ng/mL in aseptic meningoencephalitis, p = 0.010). We identified two different CSF PTX3 levels cutoffs. (1) The best cutoff to maximise Youden’s J was 9.6 ng/mL with a sensitivity, specificity, positive predictive value and negative predictive value (NPV) of 71.4%, 91.4%, 83.3%, 84.6%, respectively. (2) The cutoff with higher NPV (100%) was 3.6 ng/mL; a diagnosis of bacterial infections was obtained in 0% patients with CSF PTX3 levels < 3.6 ng/mL vs 58% of those with CSF PTX3 levels ≥ 3.6 ng/mL (p = 0.017). CSF PTX3 levels are higher in bacterial meningitis than aseptic meningoencephalitis. A cutoff of 3.6 ng/mL of CSF PTX3 has a high NPV and can be used to exclude bacterial CNS infections.
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driver mutations jak2v617f mplw515l k or calr Pentraxin 3 and c reactive protein in essential thrombocythemia and polycythemia vera
Journal of Hematology & Oncology, 2017Co-Authors: Federico Lussana, Tiziano Barbui, Alessandro M Vannucchi, Alberto Mantovani, Alessandra Carobbio, Paola Guglielmelli, Silvia Salmoiraghi, Barbara Bottazzi, Roberto Leone, Alessandro RambaldiAbstract:Background The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs.
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Pentraxin 3 in chronic heart failure the corona and gissi hf trials
European Journal of Heart Failure, 2012Co-Authors: Roberto Latini, Ivan Cuccovillo, Barbara Bottazzi, Thor Ueland, Lars Gullestad, Serge Masson, Stale H Nymo, Mari Vardal, Alberto MantovaniAbstract:Aims Pentraxin-3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF. Methods and results Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI-Heart Failure trial (GISSI-HF). The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors, high sensitivity C-reactive protein (hsCRP), and N-terminal pro brain natriuretic peptide (NT-proBNP). PTX3 concentration [median (Q1–Q3) = 5.34 (3.55–7.64) ng/mL, n = 2690] was higher in females, in older patients, and those with lower body mass index. Baseline elevated PTX3 was associated with a higher risk of all-cause mortality [759 events, hazard ratio (HR) for 1 SD increase 1.20, 95% confidence interval (CI) 1.12–1.30, P < 0.0001], cardiovascular mortality (587 events, HR 1.27, 95% CI 1.17–1.38, P < 0.0001), or hospitalization for worsening HF (720 events, HR 1.21, 95% CI 1.12–1.30, P < 0.0001), and marginally improved discrimination. Three-month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT-proBNP. Rosuvastatin lowered hsCRP levels but significantly raised PTX3. Conclusion In two independent clinical trials that enrolled patients with chronic HF, PTX3 was consistently associated with outcomes. The opposite effects of a statin on hsCRP and PTX3 call for further investigation. Trial registration NCT00336336 (GISSI-HF), NCT00206310 (CORONA).
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plasma levels of Pentraxin 3 an acute phase protein are increased during sickle cell painful crisis
Blood Cells Molecules and Diseases, 2011Co-Authors: Erfan Nur, Alberto Mantovani, Ivan Cuccovillo, Dees P M Brandjes, Eduard J Van Beers, Shuena Martina, Hansmartin Otten, J B Schnog, Joost C M Meijers, Barbara BottazziAbstract:Abstract The painful crisis accounts for the majority of sickle cell disease (SCD) related hospital admissions. The prototypic long Pentraxin 3 (PTX3), an acute phase protein, is elevated in patients with inflammatory and ischemic states. As the sickle cell painful crisis is associated with both inflammation and tissue ischemia, we questioned whether plasma PTX3 levels are increased during and associated with painful crisis severity. Furthermore, since PTX3 up-regulates endothelial expression of tissue factor we studied PTX levels in relation to markers of endothelial and coagulation activation. Plasma levels of PTX3, ultra-sensitive C-reactive protein (US-CRP), prothrombin fragment 1 + 2, thrombin–antithrombin (TAT) complexes, von Willebrand Factor antigen and soluble vascular adhesion molecule-1 were determined in 105 asymptomatic sickle cell patients, 33 patients during painful crisis and 30 race matched healthy controls. Plasma PTX3 levels were comparable between patients in asymptomatic state and healthy controls, but significantly higher during painful crisis ( P P P r s = 0.43; P = 0.013), whereas US-CRP levels did not. PTX3 levels did not correlate with markers of hypercoagulability. The increase of PTX3 levels during painful crisis and their relation to the duration of subsequent hospital stay suggest that PTX3 might serve both as a diagnostic and severity marker of the painful sickle cell crisis.
Ivan Cuccovillo - One of the best experts on this subject based on the ideXlab platform.
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Pentraxin 3 ptx3 plasma levels and carotid intima media thickness progression in the general population
Nutrition Metabolism and Cardiovascular Diseases, 2014Co-Authors: Andrea Baragetti, Alberto Mantovani, Ivan Cuccovillo, Michael Knoflach, Stefan Kiechl, Liliana Grigore, Manuela Casula, K Garlaschelli, Georg Wick, Johann WilleitAbstract:Abstract Background and aim Pentraxin 3 (PTX3) is an essential component of the humoral arm of innate immunity and, like C-reactive protein, is independently associated with the risk of developing vascular events. Aim of this study was to investigate, in two large population-based surveys, the Bruneck Study and the PLIC Study, whether PTX3 plasma levels predict the progression of common carotid artery intima–media thickness (CCA-IMT), a surrogate marker of atherosclerosis, in the general population during 5 or 6 years of follow-up. Results In the Bruneck Study, PTX3 plasma levels did not predict a faster progression of CCA-IMT either in the carotid artery or in the femoral artery. This finding was confirmed in the PLIC Study where subjects within the highest tertile of PTX3 did not show an increased progression of CCA-IMT. PTX3 plasma levels were also not associated with the fastest maximum IMT progression. In summary, in more than 2400 subjects from the general population, PTX3 plasma level is neither an independent predictor of progression of subclinical atherosclerosis in different arterial territories, including carotid and femoral arteries nor of incident cardiovascular events. Conclusion These findings support the relevance of investigating the predictive value of PTX3 plasma levels only in specific settings, like overt CVD, heart failure or acute myocardial infarction.
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Pentraxin 3 in chronic heart failure the corona and gissi hf trials
European Journal of Heart Failure, 2012Co-Authors: Roberto Latini, Ivan Cuccovillo, Barbara Bottazzi, Thor Ueland, Lars Gullestad, Serge Masson, Stale H Nymo, Mari Vardal, Alberto MantovaniAbstract:Aims Pentraxin-3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF. Methods and results Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI-Heart Failure trial (GISSI-HF). The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors, high sensitivity C-reactive protein (hsCRP), and N-terminal pro brain natriuretic peptide (NT-proBNP). PTX3 concentration [median (Q1–Q3) = 5.34 (3.55–7.64) ng/mL, n = 2690] was higher in females, in older patients, and those with lower body mass index. Baseline elevated PTX3 was associated with a higher risk of all-cause mortality [759 events, hazard ratio (HR) for 1 SD increase 1.20, 95% confidence interval (CI) 1.12–1.30, P < 0.0001], cardiovascular mortality (587 events, HR 1.27, 95% CI 1.17–1.38, P < 0.0001), or hospitalization for worsening HF (720 events, HR 1.21, 95% CI 1.12–1.30, P < 0.0001), and marginally improved discrimination. Three-month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT-proBNP. Rosuvastatin lowered hsCRP levels but significantly raised PTX3. Conclusion In two independent clinical trials that enrolled patients with chronic HF, PTX3 was consistently associated with outcomes. The opposite effects of a statin on hsCRP and PTX3 call for further investigation. Trial registration NCT00336336 (GISSI-HF), NCT00206310 (CORONA).
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Pentraxin 3 as a marker of advanced atherosclerosis results from the bruneck army and arfy studies
PLOS ONE, 2012Co-Authors: Michael Knoflach, Alberto Mantovani, Ivan Cuccovillo, Stefan Kiechl, Qingzhong Xiao, Arno Gasperi, Agnes Mayr, Marlene Kehrer, Johann WilleitAbstract:Objective Pentraxins like C-reactive protein are key components of the innate immune system. Recently, Pentraxin-3 (PTX3) has been proposed to be a specific marker of vascular inflammation, yet its association with atherosclerosis is still unclear.
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plasma levels of Pentraxin 3 an acute phase protein are increased during sickle cell painful crisis
Blood Cells Molecules and Diseases, 2011Co-Authors: Erfan Nur, Alberto Mantovani, Ivan Cuccovillo, Dees P M Brandjes, Eduard J Van Beers, Shuena Martina, Hansmartin Otten, J B Schnog, Joost C M Meijers, Barbara BottazziAbstract:Abstract The painful crisis accounts for the majority of sickle cell disease (SCD) related hospital admissions. The prototypic long Pentraxin 3 (PTX3), an acute phase protein, is elevated in patients with inflammatory and ischemic states. As the sickle cell painful crisis is associated with both inflammation and tissue ischemia, we questioned whether plasma PTX3 levels are increased during and associated with painful crisis severity. Furthermore, since PTX3 up-regulates endothelial expression of tissue factor we studied PTX levels in relation to markers of endothelial and coagulation activation. Plasma levels of PTX3, ultra-sensitive C-reactive protein (US-CRP), prothrombin fragment 1 + 2, thrombin–antithrombin (TAT) complexes, von Willebrand Factor antigen and soluble vascular adhesion molecule-1 were determined in 105 asymptomatic sickle cell patients, 33 patients during painful crisis and 30 race matched healthy controls. Plasma PTX3 levels were comparable between patients in asymptomatic state and healthy controls, but significantly higher during painful crisis ( P P P r s = 0.43; P = 0.013), whereas US-CRP levels did not. PTX3 levels did not correlate with markers of hypercoagulability. The increase of PTX3 levels during painful crisis and their relation to the duration of subsequent hospital stay suggest that PTX3 might serve both as a diagnostic and severity marker of the painful sickle cell crisis.
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persisting high levels of plasma Pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality
Intensive Care Medicine, 2010Co-Authors: Tommaso Mauri, Giuseppe Peri, Ivan Cuccovillo, Andrea Coppadoro, Giacomo Bellani, Nicolò Patroniti, Massimo Cugno, Gaetano Iapichino, Luciano Gattinoni, Antonio PesentiAbstract:Purpose Pentraxin 3 (PTX3) is an inflammatory mediator produced by neutrophils, macrophages, myeloid dendritic and endothelial cells. During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur. PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis.
Takakuni Maki - One of the best experts on this subject based on the ideXlab platform.
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biphasic roles of Pentraxin 3 in cerebrovascular function after white matter stroke
CNS Neuroscience & Therapeutics, 2021Co-Authors: Akihiro Shindo, Takakuni Maki, Emiri T Mandeville, Naohiro Egawa, Hajime Takase, Gen Hamanaka, Kelly K ChungAbstract:Recent clinical studies suggest that Pentraxin 3 (PTX3), which is known as an acute-phase protein that is produced rapidly at local sites of inflammation, may be a new biomarker of disease risk for central nervous system disorders, including stroke. However, the effects of PTX3 on cerebrovascular function in the neurovascular unit (NVU) after stroke are mostly unknown, and the basic research regarding the roles of PTX3 in NVU function is still limited. In this reverse translational study, we prepared mouse models of white matter stroke by vasoconstrictor (ET-1 or L-Nio) injection into the corpus callosum region to examine the roles of PTX3 in the pathology of cerebral white matter stroke. PTX3 expression was upregulated in GFAP-positive astrocytes around the affected region in white matter for at least 21 days after vasoconstrictor injection. When PTX3 expression was reduced by PTX3 siRNA, blood-brain barrier (BBB) damage at day 3 after white matter stroke was exacerbated. In contrast, when PTX3 siRNA was administered at day 7 after white matter stroke, compensatory angiogenesis at day 21 was promoted. In vitro cell culture experiments confirmed the inhibitory effect of PTX3 in angiogenesis, that is, recombinant PTX3 suppressed the tube formation of cultured endothelial cells in a Matrigel-based in vitro angiogenesis assay. Taken together, our findings may support a novel concept that astrocyte-derived PTX3 plays biphasic roles in cerebrovascular function after white matter stroke; additionally, it may also provide a proof-of-concept that PTX3 could be a therapeutic target for white matter-related diseases, including stroke.
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astrocyte derived Pentraxin 3 supports blood brain barrier integrity under acute phase of stroke
Stroke, 2016Co-Authors: Akihiro Shindo, Takakuni Maki, Emiri T Mandeville, Anna C Liang, Naohiro Egawa, Kanako Itoh, Naoki Itoh, Mia C Borlongan, Julie C Holder, Tsu Tshen ChuangAbstract:Background and Purpose—Pentraxin 3 (PTX3) is released on inflammatory responses in many organs. However, roles of PTX3 in brain are still mostly unknown. Here we asked whether and how PTX3 contribu...