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Article ; Online: Long Pentraxin 3 as a New Biomarker for Diagnosis of Hip and Knee Periprosthetic Joint Infections

Mattia Loppini / Marco Di Maio / Roberta Avigni / Roberto Leone / Antonio Inforzato / Guido Grappiolo / Alberto Mantovani / Barbara Bottazzi

Journal of Clinical Medicine, Vol 12, Iss 1055, p

2023 Volume 1055

Abstract: Background: Preoperative diagnosis of periprosthetic joint infections (PJIs) poses an unmet clinical challenge. The long pentraxin PTX3 is a component of the innate immune system involved in infection immunity. This study evaluated the potential of ... ...

Abstract	Background: Preoperative diagnosis of periprosthetic joint infections (PJIs) poses an unmet clinical challenge. The long pentraxin PTX3 is a component of the innate immune system involved in infection immunity. This study evaluated the potential of synovial and plasmatic PTX3 in the diagnosis of hip and knee PJIs. Methods: Consecutive total hip and knee arthroplasty (THA/TKA) revisions were prospectively included and classified as septic or aseptic according to the European Bone and Joint Infection Society (EBJIS) and Musculoskeletal Infection Society (MSIS) criteria. The concentration of PTX3 in plasma and synovial fluid samples was measured with ELISA. The AUC, threshold value, sensitivity, specificity, and positive and negative likelihood ratios were calculated using the ROC (receiver operating characteristic) curve method. Results: The study population included 128 patients (94 THAs; 34 TKAs). The AUC of the synovial PTX3 based on EBJIS criteria was 0.85 ( p < 0.0001), with a sensitivity of 81.13% and a specificity of 93.33%. The AUC based on MSIS criteria was 0.95 ( p < 0.001), with a sensitivity of 91.43% and a specificity of 89.25%. Plasmatic PTX3 failed to discriminate infected from non-infected patients. Conclusions: Synovial PTX3 demonstrated an excellent diagnostic potential in hip and knee PJIs, with a very high specificity irrespective of the diagnostic criteria for PJI.
Keywords	periprosthetic joint infections ; hip ; knee ; pentraxin 3 ; biomarkers ; Medicine ; R
Subject code	796
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetic Deficiency of the Long Pentraxin 3 Affects Osteogenesis and Osteoclastogenesis in Homeostatic and Inflammatory Conditions

Valentina Granata / Dario Strina / Maria Lucia Schiavone / Barbara Bottazzi / Alberto Mantovani / Antonio Inforzato / Cristina Sobacchi

International Journal of Molecular Sciences, Vol 24, Iss 23, p

2023 Volume 16648

Abstract: The long pentraxin 3 (PTX3) is a soluble glycoprotein made by immune and nonimmune cells endowed with pleiotropic functions in innate immunity, inflammation, and tissue remodeling. PTX3 has recently emerged as a mediator of bone turnover in both ... ...

Abstract	The long pentraxin 3 (PTX3) is a soluble glycoprotein made by immune and nonimmune cells endowed with pleiotropic functions in innate immunity, inflammation, and tissue remodeling. PTX3 has recently emerged as a mediator of bone turnover in both physiological and pathological conditions, with direct and indirect effects on osteoblasts and osteoclasts. This notwithstanding, its role in bone biology, with major regard to the osteogenic potential of osteoblasts and their interplay with osteoclasts, is at present unclear. Here, we investigated the contribution of this pentraxin to bone deposition in the osteogenic lineage by assessing collagen production, mineralization capacity, osteoblast maturation, extracellular matrix gene expression, and inflammatory mediators’ production in primary osteoblasts from the calvaria of wild-type (WT) and Ptx3 -deficient ( Ptx3 −/− ) mice. Also, we evaluated the effect of PTX3 on osteoclastogenesis in cocultures of primary osteoblasts and bone marrow-derived osteoclasts. Our investigations were carried out both in physiological and inflammatory conditions to recapitulate in vitro aspects of inflammatory diseases of the bone. We found that primary osteoblasts from WT animals constitutively expressed low levels of the protein in osteogenic noninflammatory conditions, and genetic ablation of PTX3 in these cells had no major impact on collagen and hydroxyapatite deposition. However, Ptx3 −/− osteoblasts had an increased RANKL/OPG ratio and CD44 expression, which resulted in in enhanced osteoclastogenesis when cocultured with bone marrow monocytes. Inflammation (modelled through administration of tumor necrosis factor-α, TNF-α) boosted the expression and accumulation of PTX3 and inflammatory mediators in WT osteoblasts. In these conditions, Ptx3 genetic depletion was associated with reduced collagen deposition and immune modulators’ production. Our study shed light on the role of PTX3 in osteoblast and osteoclast biology and identified a major effect of inflammation on the bone-related ...
Keywords	osteoblast ; osteoclast ; PTX3 ; bone ; tissue remodeling ; hyaluronan-rich matrix ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3

Rémi Porte / Rita Silva-Gomes / Charlotte Theroude / Raffaella Parente / Fatemeh Asgari / Marina Sironi / Fabio Pasqualini / Sonia Valentino / Rosanna Asselta / Camilla Recordati / Marta Noemi Monari / Andrea Doni / Antonio Inforzato / Carlos Rodriguez-Gallego / Ignacio Obando / Elena Colino / Barbara Bottazzi / Alberto Mantovani

eLife, Vol

2023 Volume 12

Abstract: Streptococcus pneumoniae is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of ... ...

Abstract	Streptococcus pneumoniae is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to assess the role of PTX3 in invasive pneumococcal infection. In a murine model of invasive pneumococcal infection, PTX3 was strongly induced in non-hematopoietic (particularly, endothelial) cells. The IL-1β/MyD88 axis played a major role in regulation of the Ptx3 gene expression. Ptx3−/− mice presented more severe invasive pneumococcal infection. Although high concentrations of PTX3 had opsonic activity in vitro, no evidence of PTX3-enhanced phagocytosis was obtained in vivo. In contrast, Ptx3-deficient mice showed enhanced recruitment of neutrophils and inflammation. Using P-selectin-deficient mice, we found that protection against pneumococcus was dependent upon PTX3-mediated regulation of neutrophil inflammation. In humans, PTX3 gene polymorphisms were associated with invasive pneumococcal infections. Thus, this fluid-phase PRM plays an important role in tuning inflammation and resistance against invasive pneumococcal infection.
Keywords	Streptococcus pneumoniae ; Pentraxin 3 ; neutrophils ; inflammation ; P-selectin ; endothelial cells ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
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Article ; Online: 3D Cocultures of Osteoblasts and Staphylococcus aureus on Biomimetic Bone Scaffolds as a Tool to Investigate the Host–Pathogen Interface in Osteomyelitis

Raffaella Parente / Valentina Possetti / Maria Lucia Schiavone / Elisabetta Campodoni / Ciro Menale / Mattia Loppini / Andrea Doni / Barbara Bottazzi / Alberto Mantovani / Monica Sandri / Anna Tampieri / Cristina Sobacchi / Antonio Inforzato

Pathogens, Vol 10, Iss 837, p

2021 Volume 837

Abstract: Osteomyelitis (OM) is an infectious disease of the bone primarily caused by the opportunistic pathogen Staphylococcus aureus (SA). This Gram-positive bacterium has evolved a number of strategies to evade the immune response and subvert bone homeostasis, ... ...

Abstract	Osteomyelitis (OM) is an infectious disease of the bone primarily caused by the opportunistic pathogen Staphylococcus aureus (SA). This Gram-positive bacterium has evolved a number of strategies to evade the immune response and subvert bone homeostasis, yet the underlying mechanisms remain poorly understood. OM has been modeled in vitro to challenge pathogenetic hypotheses in controlled conditions, thus providing guidance and support to animal experimentation. In this regard, traditional 2D models of OM inherently lack the spatial complexity of bone architecture. Three-dimensional models of the disease overcome this limitation; however, they poorly reproduce composition and texture of the natural bone. Here, we developed a new 3D model of OM based on cocultures of SA and murine osteoblastic MC3T3-E1 cells on magnesium-doped hydroxyapatite/collagen I (MgHA/Col) scaffolds that closely recapitulate the bone extracellular matrix. In this model, matrix-dependent effects were observed in proliferation, gene transcription, protein expression, and cell–matrix interactions both of the osteoblastic cell line and of bacterium. Additionally, these had distinct metabolic and gene expression profiles, compared to conventional 2D settings, when grown on MgHA/Col scaffolds in separate monocultures. Our study points to MgHA/Col scaffolds as biocompatible and bioactive matrices and provides a novel and close-to-physiology tool to address the pathogenetic mechanisms of OM at the host–pathogen interface.
Keywords	Staphylococcus aureus ; osteomyelitis ; osteoblast-like cells ; host–pathogen interface ; 3D models ; biomimetic bone scaffolds ; Medicine ; R
Subject code	616
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Circulating biomarkers in familial cerebral cavernous malformationResearch in context

Francesca Lazzaroni / Jennifer M.T.A. Meessen / Ying Sun / Silvia Lanfranconi / Elisa Scola / Quintino Giorgio D'Alessandris / Laura Tassi / Maria Rita Carriero / Marco Castori / Silvia Marino / Adriana Blanda / Enrico B. Nicolis / Deborah Novelli / Roberta Calabrese / Nicolò M. Agnelli / Barbara Bottazzi / Roberto Leone / Selene Mazzola / Silvia Besana /

Carlotta Catozzi / Luigi Nezi / Maria G. Lampugnani / Matteo Malinverno / Nastasja Grdseloff / Claudia J. Rödel / Behnam Rezai Jahromi / Niccolò Bolli / Francesco Passamonti / Peetra U. Magnusson / Salim Abdelilah-Seyfried / Elisabetta Dejana / Roberto Latini

EBioMedicine, Vol 99, Iss , Pp 104914- (2024)

1481

Abstract: Summary: Background: Cerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICHs), seizure(s), or focal neurological deficits ...

Abstract	Summary: Background: Cerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICHs), seizure(s), or focal neurological deficits (FND). Familial CCM (fCCM) is due to loss of function mutations in one of the three independent genes KRIT1 (CCM1), Malcavernin (CCM2), or Programmed Cell death 10 (PDCD10/CCM3). The aim of this study was to identify plasma protein biomarkers of fCCM to assess the severity of the disease and predict its progression. Methods: Here, we have investigated plasma samples derived from n = 71 symptomatic fCCM patients (40 female/31 male) and n = 17 healthy donors (HD) (9 female/8 male) of the Phase 1/2 Treat_CCM trial, using multiplexed protein profiling approaches. Findings: Biomarkers as sCD14 (p = 0.00409), LBP (p = 0.02911), CXCL4 (p = 0.038), ICAM-1 (p = 0.02013), ANG2 (p = 0.026), CCL5 (p = 0.00403), THBS1 (p = 0.0043), CRP (p = 0.0092), and HDL (p = 0.027), were significantly different in fCCM compared to HDs. Of note, sENG (p = 0.011), THBS1 (p = 0.011) and CXCL4 (p = 0.011), were correlated to CCM genotype. sROBO4 (p = 0.014), TM (p = 0.026) and CRP (p = 0.040) were able to predict incident adverse clinical events, such as ICH, FND or seizure. GDF-15, FLT3L, CXCL9, FGF-21 and CDCP1, were identified as predictors of the formation of new MRI-detectable lesions over 2-year follow-up. Furthermore, the functional relevance of ang2, thbs1, robo4 and cdcp1 markers was validated by zebrafish pre-clinical model of fCCM. Interpretation: Overall, our study identifies a set of biochemical parameters to predict CCM progression, suggesting biological interpretations and potential therapeutic approaches to CCM disease. Funding: Italian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro (AIRC), ERC, Leducq Transatlantic Network of Excellence, Swedish Research Council.
Keywords	Familial cerebral cavernous malformation ; Vascular biology ; Biomarkers ; Proteomics ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Serum amyloid P component is an essential element of resistance against Aspergillus fumigatus

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 15

Abstract: Serum Amyloid P is a humoral component with established roles in the response to bacterial infection and regulation of tissue remodeling. Here the authors provide evidence to a further crucial role of serum amyloid P in the context of fungal pathogen ... ...

Abstract	Serum Amyloid P is a humoral component with established roles in the response to bacterial infection and regulation of tissue remodeling. Here the authors provide evidence to a further crucial role of serum amyloid P in the context of fungal pathogen Aspergillus fumigatus.
Keywords	Science ; Q
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A New Surface Plasmon Resonance-Based Immunoassay for Rapid, Reproducible and Sensitive Quantification of Pentraxin-3 in Human Plasma

Mara Canovi / Jacopo Lucchetti / Matteo Stravalaci / Sonia Valentino / Barbara Bottazzi / Mario Salmona / Antonio Bastone / Marco Gobbi

Sensors, Vol 14, Iss 6, Pp 10864-

2014 Volume 10875

Abstract: A new immunoassay based on surface plasmon resonance (SPR) for the rapid, reproducible and sensitive determination of pentraxin-3 (PTX3) levels in human plasma has been developed and characterized. The method involves a 3-min flow of plasma over a sensor ...

Abstract	A new immunoassay based on surface plasmon resonance (SPR) for the rapid, reproducible and sensitive determination of pentraxin-3 (PTX3) levels in human plasma has been developed and characterized. The method involves a 3-min flow of plasma over a sensor chip pre-coated with a monoclonal anti-PTX3 antibody (MNB4), followed by a 3-min flow of a polyclonal anti-PTX3 antibody (pAb), required for specific recognition of captured PTX3. The SPR signal generated with this secondary antibody linearly correlates with the plasma PTX3 concentration, in the range of 5–1500 ng/mL, with a lowest limit of detection of 5 ng/mL. The PTX3 concentrations determined with the SPR-based immunoassay in the plasma of 21 patients with sepsis, ranging 15–1600 ng/mL, were superimposable to those found in a classic ELISA immunoassay. Since the PTX3 concentration in the plasma of healthy subjects is <2 ng/mL, but markedly rises in certain medical conditions, the method is useful to quantify pathological levels of this important biomarker, with important diagnostic applications. In comparison with the classic ELISA, the SPR-based approach is much faster (30 min versus 4–5 h) and could be exploited for the development of new cost-effective SPR devices for point-of-care diagnosis.
Keywords	surface plasmon resonance ; SPR-based immunoassay ; pentraxin-3 ; plasma ; sepsis ; Technology (General) ; T1-995 ; Technology ; T ; Analytical chemistry ; QD71-142 ; Chemistry ; QD1-999 ; Science ; Q
Subject code	600
Language	English
Publishing date	2014-06-01T00:00:00Z
Publisher	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pathogen Recognition by the Long Pentraxin PTX3

Federica Moalli / Sebastien Jaillon / Antonio Inforzato / Marina Sironi / Barbara Bottazzi / Alberto Mantovani / Cecilia Garlanda

Journal of Biomedicine and Biotechnology, Vol

2011 Volume 2011

Abstract: Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm ... ...

Abstract	Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognise pathogen-associated molecular patterns (PAMPs) and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a nonredundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the cross-road between innate immunity, inflammation, and female fertility. Here, we review the studies on PTX3, with emphasis on pathogen recognition and cross-talk with other components of the innate immune system.
Keywords	Biotechnology ; TP248.13-248.65 ; Medicine ; R
Subject code	570
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Anti-rheumatic treatment is not associated with reduction of pentraxin 3 in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

Gia Deyab / Ingrid Hokstad / Jon Elling Whist / Milada Cvancarova Småstuen / Stefan Agewall / Torstein Lyberg / Barbara Bottazzi / Pier Luigi Meroni / Roberto Leone / Gunnbjorg Hjeltnes / Ivana Hollan

PLoS ONE, Vol 12, Iss 2, p e

2017 Volume 0169830

Abstract: BACKGROUND:Pentraxin 3 is proposed to be a marker of inflammation and cardiovascular risk, but its role in inflammatory rheumatic diseases (IRDs) is still uncertain. Therefore, we wanted to examine if anti-rheumatic treatment reduced serum PTX3 (s-PTX3) ... ...

Abstract	BACKGROUND:Pentraxin 3 is proposed to be a marker of inflammation and cardiovascular risk, but its role in inflammatory rheumatic diseases (IRDs) is still uncertain. Therefore, we wanted to examine if anti-rheumatic treatment reduced serum PTX3 (s-PTX3) levels in IRDs, and if s-PTX3 levels were related to other markers of inflammation and to endothelial function (EF). METHODS:We examined s-PTX3, EF and established inflammatory biomarkers in 114 IRD patients from the PSARA study before and after 6 weeks and 6 months of treatment with methotrexate (MTX) or anti-tumor necrosis factor alpha (anti-TNF) therapy with or without MTX co-medication. RESULTS:s-PTX3 levels in all IRD diagnoses were above the upper limit of the reference range. In contrast to established inflammatory markers, in particular CRP and ESR, s-PTX3 levels did not change significantly after 6 weeks and 6 months of anti-rheumatic therapy. There was no difference in change in s-PTX3 levels from baseline to 6 weeks and 6 months between MTX monotherapy and anti-TNF regimens. CRP, ESR and EF were not related to changes in s-PTX3 neither in crude nor adjusted analyses. CONCLUSION:IRD patients have increased s-PTX3 levels, which, in contrast to other inflammatory markers, do not seem to improve within 6 months of therapy with MTX and/or anti-TNF. Thus, s-PTX3 might reflect a persisting immune process, even a causal factor of inflammation, not inhibited by the standard anti-rheumatic treatment. Furthermore, even though s-PTX3 is thought to be a strong predictor of cardiovascular prognosis, it was not related to EF.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Plasma complement and vascular complement deposition in patients with coronary artery disease with and without inflammatory rheumatic diseases.

Kelly J Shields / Tom Eirik Mollnes / Jon Roger Eidet / Knut Mikkelsen / Sven M Almdahl / Barbara Bottazzi / Torstein Lyberg / Susan Manzi / Joseph M Ahearn / Ivana Hollan

PLoS ONE, Vol 12, Iss 3, p e

2017 Volume 0174577

Abstract: PURPOSE:Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of ... ...

Abstract	PURPOSE:Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients. METHODS:We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry. RESULTS:IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (p<0.0001), but a similar p-C3 level (p = 0.42). Circulating C3 was associated with IRD duration (ρ, p-value: 0.46, 0.03). In multiple logistic regression analysis, IRD remained significantly related to the presence and size of MCI (p<0.05). C3 was present in all tissue samples. C3d was detected in the media of all patients and only in the adventitia of IRD patients (diffuse in all SLE and focal in one RA). CONCLUSION:The independent association of IRD status with MCI and the observed C3d deposition supports the unique relationship between rheumatic disease, and, in particular, SLE with the complement system. Exaggerated systemic and vascular complement activation may accelerate CVD, serve as a CVD biomarker, and ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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