Evidence map›Paper›PMID 40238197›Full record

ArticleRheumatology (Oxford, England)2025

Anti-β2glycoprotein I-induced neutrophil extracellular traps cause endothelial activation.

Silvia Mancuso, Mattia Caliste, Andrea Petretto, Elisa Corsiero, Nicole Grinovero, Antonella Capozzi, Gloria Riitano, Cristiana Barbati, Simona Truglia, Cristiano Alessandri and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Rheumatology (Oxford, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Silvia MancusoRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
Mattia CalisteRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
Andrea PetrettoCore Facilities-Clinical Proteomics and Metabolomics, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Elisa CorsieroCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), London, UK.
Nicole GrinoveroCore Facilities-Clinical Proteomics and Metabolomics, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Antonella CapozziDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Gloria RiitanoDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Cristiana BarbatiRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
Simona TrugliaRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
Cristiano AlessandriRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.ORCID 0000-0003-4149-5321
Maurizio SoriceDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0000-0003-3534-1502
Michele BombardieriCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), London, UK.
Fabrizio ContiRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveNeutrophil extracellular traps (NETs) involvement in antiphospholipid syndrome (APS) pathogenesis is known, but the role of anti-β2glycoprotein I (aβ2GPI) antibodies-induced NETs in triggering a procoagulant and proinflammatory phenotype in endothelial cells (ECs) remains to be evaluated. This study investigated whether NET-aβ2GPI can activate ECs and whether NET-aβ2GPI and NET-phorbol myristate acetate (PMA) have different proteomic profiles.

methodsHealthy donor (HD) neutrophils were stimulated with APS-aβ2GPI, normal human IgG or PMA. NETs were stained with anti-neutrophil elastase and 4'6-diamidino-2-phenylindole (DAPI), and the ability of aβ2GPI to bind NETs and inhibit DNA degradation was investigated. Following aβ2GPI, NET-aβ2GPI and NET-PMA stimuli, we evaluated EC activation investigating intra-cellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and tissue factor (TF) expression using flow cytometry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR); and EC dysfunction analysing extracellular microvesicles (EMVs) release via flow cytometry and NanoSight analysis. Mass spectrometry-based proteomics was performed on NET-aβ2GPI and NET-PMA.

resultsUnlike normal IgG, aβ2GPI induced NET formation and bound to NETs by colocalizing with the neutrophil elastase signal at 93.6% without preventing NET degradation. Compared with unstimulated EC, NET-aβ2GPI triggered higher mRNA and a robust expression of TF, VCAM and ICAM in EC with a change-fold median fluorescence intensity (MFI) of 6, 4.2 and 2.3. aβ2GPI induced a significant increase in EMVs compared with untreated samples and those treated with NETs. Fifty-six proteins were identified, seven resulted upregulated in NET-aβ2GPI and downregulated in PMA-induced ones. GO enrichment analysis revealed that proteins upregulated in NET-aβ2GPI were enriched for ubiquitin protein ligase binding and SLC2A4 translocation to the plasma membrane.

conclusionaβ2GPI-induced NETs can cause EC activation and TF expression.

Indexed as

Antiphospholipid Syndromebeta 2-Glycoprotein IEndothelial CellsExtracellular TrapsNeutrophilsHumansProteomicsThromboplastinVascular Cell Adhesion Molecule-1beta 2-Glycoprotein IThromboplastinVascular Cell Adhesion Molecule-1anti-β2glycoprotein Iendothelial cell activationNET formation

Identifiers

PMID40238197
PMCPMC12316379

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.