Evidence map›Paper›PMID 38609158›Full record

ArticleAnnals of the rheumatic diseases2024

Disentangling the riddle of systemic lupus erythematosus with antiphospholipid syndrome: blood transcriptome analysis reveals a less-pronounced IFN-signature and distinct molecular profiles in venous versus arterial events.

Dionysis Nikolopoulos, Catherine Loukogiannaki, George Sentis, Panagiotis Garantziotis, Theodora Manolakou, Noemin Kapsala, Myrto Nikoloudaki, Antigone Pieta, Sofia Flouda, Ioannis Parodis and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
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

15 citing papers in PubMed, 16 citations in OpenAlex.

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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

14 authors at 5 institutions in 4 countries.

Dionysis NikolopoulosClinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece dsnikolopoulos@gmail.com boumpasd@uoc.gr.ORCID http://orcid.org/0000-0002-9894-6966
Catherine Loukogiannaki *Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.ORCID http://orcid.org/0009-0005-6989-1790
George Sentis *Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Panagiotis Garantziotis *Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Theodora ManolakouClinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.ORCID http://orcid.org/0000-0001-5284-6655
Noemin Kapsala4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Myrto NikoloudakiRheumatology, University of Crete School of Medicine, Iraklio, Crete, Greece.
Antigone Pieta4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Sofia Flouda4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Ioannis ParodisDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-4875-5395
George BertsiasRheumatology, University of Crete School of Medicine, Iraklio, Crete, Greece.ORCID http://orcid.org/0000-0001-5299-1406
Antonis FanouriakisClinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.ORCID http://orcid.org/0000-0003-2696-031X
Anastasia FiliaClinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.ORCID http://orcid.org/0000-0003-3824-2745
Dimitrios T BoumpasClinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece dsnikolopoulos@gmail.com boumpasd@uoc.gr.ORCID http://orcid.org/0000-0002-9812-4671
National and Kapodistrian University of Athens · GRAcademy of Athens · GRUniversity of Crete · GRÖrebro University · SEUniversity of Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionSystemic lupus erythematosus with antiphospholipid syndrome (SLE-APS) represents a challenging SLE endotype whose molecular basis remains unknown.

methodsWe analysed whole-blood RNA-sequencing data from 299 patients with SLE (108 SLE-antiphospholipid antibodies (aPL)-positive, including 67 SLE-APS; 191 SLE-aPL-negative) and 72 matched healthy controls (HC). Pathway enrichment analysis, unsupervised weighted gene coexpression network analysis and machine learning were applied to distinguish disease endotypes.

resultsPatients with SLE-APS demonstrated upregulated type I and II interferon (IFN) pathways compared with HC. Using a 100-gene random forests model, we achieved a cross-validated accuracy of 75.6% in distinguishing these two states. Additionally, the comparison between SLE-APS and SLE-aPL-negative revealed 227 differentially expressed genes, indicating downregulation of IFN-α and IFN-γ signatures, coupled with dysregulation of the complement cascade, B-cell activation and neutrophil degranulation. Unsupervised analysis of SLE transcriptome identified 21 gene modules, with SLE-APS strongly linked to upregulation of the 'neutrophilic/myeloid' module. Within SLE-APS, venous thromboses positively correlated with 'neutrophilic/myeloid' and 'B cell' modules, while arterial thromboses were associated with dysregulation of 'DNA damage response (DDR)' and 'metabolism' modules. Anticardiolipin and anti-β2GPI positivity-irrespective of APS status-were associated with the 'neutrophilic/myeloid' and 'protein-binding' module, respectively.

conclusionsThere is a hierarchical upregulation and-likely-dependence on IFN in SLE with the highest IFN signature observed in SLE-aPL-negative patients. Venous thrombotic events are associated with neutrophils and B cells while arterial events with DDR and impaired metabolism. This may account for their differential requirements for anticoagulation and provide rationale for the potential use of mTOR inhibitors such as sirolimus and the direct fIIa inhibitor dabigatran in SLE-APS.

Indexed as

Antiphospholipid SyndromeGene Expression ProfilingLupus Erythematosus, SystemicTranscriptomeAdultAntibodies, AntiphospholipidCase-Control StudiesFemaleHumansInterferonsMaleMiddle AgedVenous ThrombosisAntibodies, AntiphospholipidInterferonsAntibodies, AntiphospholipidAntiphospholipid SyndromeLupus Erythematosus, SystemicThrombosis

Identifiers

PMID38609158
PMCPMC11420729
OpenAlexW4394769181

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.