Evidence map›Paper›PMID 41399015›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2026

Molecular Stratification of Antiphospholipid Syndrome Through Integrative Analysis of the Whole-Blood RNA Transcriptome.

Amala Ambati, Feiyang Ma, Katarina Kmetova, Sherwin Navaz, Claire K Hoy, Cyrus Sarosh, Ajay Tambralli, Erika Navarro-Mendoza, Johann E Gudjonsson, J Michelle Kahlenberg and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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.

Amala AmbatiDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.
Feiyang MaDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.
Katarina KmetovaDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.ORCID 0000-0002-2730-4587
Sherwin NavazDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.
Claire K HoyDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.
Cyrus SaroshDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.
Ajay TambralliDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.
Erika Navarro-MendozaDepartment of Rheumatology, Mayo Clinic, Rochester, Minnesota.
Johann E GudjonssonDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.
J Michelle KahlenbergDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.ORCID 0000-0002-4006-8945
Jacqueline A MadisonDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.
Alí Duarte-GarcíaDepartment of Rheumatology, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0003-1749-5719
Jason S KnightDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.ORCID 0000-0003-0995-9771
Yu ZuoDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.ORCID 0000-0001-6721-7755

Funding

Thromboinflammatory consequences of infection-induced autoimmunityK08AR080205 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Yu Zuo · 2022 to 2026
$865k
NIAMS NIH HHS K08 AR080205
6 · The paper itself

Abstract

objectiveAntiphospholipid syndrome (APS) is a thromboinflammatory disorder characterized by clinical and mechanistic heterogeneity that complicates early diagnosis and hinders targeted treatment. We aimed to identify distinct molecular endotypes among antiphospholipid antibody (aPL)-positive patients using whole-blood transcriptomics.

methodsWhole-blood RNA sequencing was performed on 174 aPL-positive patients, including those with primary APS (n = 102), secondary APS (n = 29), and aPL positivity without classifiable APS (n = 43). Unsupervised machine learning and immune cell deconvolution defined transcriptomic clusters and immune landscapes.

resultsFour transcriptionally distinct clusters were identified. At one end of the spectrum, cluster 1 showed up-regulation of ribosomal and metabolic pathways and down-regulation of mechanistic target of rapamycin (mTOR), NETosis, and Hippo/interleukin-6 (IL-6) signaling. In contrast, cluster 4 exhibited the opposite pattern, with strong up-regulation of mTOR, NETosis, and Hippo/IL-6 signaling. Cluster 2 demonstrated modest enrichment in messenger RNA processing and amino acid metabolism, and cluster 3 showed biosynthetic suppression with mild Hippo/IL-6 activation. Clinically, cluster 4 stood out with higher IgG anticardiolipin and anti-β

conclusionThis study reveals four endotypes of aPL-positive patients, a step toward personalized medicine for APS through pathway-informed stratification and therapy.

Indexed as

Antiphospholipid SyndromeTranscriptomeAdultAntibodies, AntiphospholipidFemaleHumansInterleukin-6MaleMiddle AgedProtein Serine-Threonine KinasesSequence Analysis, RNASignal TransductionTOR Serine-Threonine KinasesAntibodies, AntiphospholipidInterleukin-6MTOR protein, humanProtein Serine-Threonine KinasesTOR Serine-Threonine Kinases

Identifiers

PMID41399015
PMCPMC13129634

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.