A pro‐inflammatory cytokine signature characterises thrombotic antiphospholipid syndrome despite stable anticoagulation
5 affiliations
- 1Centre for Haematology, Department of Immunology and Inflammation Imperial College London London UK
- 2Department of Clinical Infection, Microbiology and Immunology University of Liverpool Liverpool UK
- 3Roald Dahl Haemostasis and Thrombosis Centre Liverpool University Hospitals NHS Foundation Trust Liverpool UK
- 4National Heart and Lung Institute Imperial College London London UK
- 5Department of Haematology Imperial College Healthcare NHS Trust London UK
Abstract
Inflammation contributes to primary antiphospholipid syndrome (PAPS) pathogenesis, but cytokine profiles and associated thrombotic phenotypes remain incompletely defined. A panel of 20 cytokines, chemokines and endothelial activation markers was analysed in 37 PAPS patients on stable anticoagulation and 12 healthy controls (HC). We compared concentrations between groups and performed unsupervised hierarchical clustering and principal component analysis (PCA) to identify inflammatory subgroups. Compared with HC, patients with PAPS exhibited significantly elevated levels of 14/20 analytes: granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interferon (IFN)‐γ, interleukin (IL)‐1α, IL‐1β, IL‐6, IL‐10, IL‐12p70, IL‐13, IL‐17a, tumour necrosis factor‐α (TNF‐α), intercellular adhesion molecule‐1 (ICAM‐1), P‐selectin and macrophage inflammatory protein‐1β (MIP1β) (all p < 0.05). Unsupervised clustering identified three inflammatory antiphospholipid syndrome (APS) subgroups distinct from HC. A core cytokine signature comprising GM‐CSF, IL‐6, IL‐10, IL‐12p70, IL‐13 and TNF‐α was elevated across all APS clusters. One cluster, enriched for arterial thrombosis, demonstrated a more pronounced inflammatory phenotype, with increased IFN‐α. Comparison of phenotypes showed significantly higher concentrations of GM‐CSF, IFN‐α, IL‐1α, IL‐4, IL‐6, IL‐10, IL‐17a and TNF‐α in arterial versus venous thrombosis. Our findings demonstrate widespread cytokine dysregulation and distinct inflammatory subgroups in PAPS, with arterial thrombosis showing stronger inflammation than venous thrombosis, supporting divergent thrombo‐inflammatory mechanisms and potential precision immunomodulatory therapeutic targets.
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BibTeX
@article{ducker2026proinflammatory,
title = {{A pro‐inflammatory cytokine signature characterises thrombotic antiphospholipid syndrome despite stable anticoagulation}},
author = {Catherine B. Ducker and Megan V. Preece and Jeremy Schofield and Charis Pericleous and Mike Laffan and Simon Abrams and Deepa J. Arachchillage},
journal = {British Journal of Haematology},
year = {2026},
month = sep,
doi = {10.1111/bjh.70816},
url = {https://doi.org/10.1111/bjh.70816},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A pro‐inflammatory cytokine signature characterises thrombotic antiphospholipid syndrome despite stable anticoagulation
AU - Catherine B. Ducker
AU - Megan V. Preece
AU - Jeremy Schofield
AU - Charis Pericleous
AU - Mike Laffan
AU - Simon Abrams
AU - Deepa J. Arachchillage
PY - 2026
DA - 2026/09/09
JO - British Journal of Haematology
DO - 10.1111/bjh.70816
UR - https://doi.org/10.1111/bjh.70816
AB - Inflammation contributes to primary antiphospholipid syndrome (PAPS) pathogenesis, but cytokine profiles and associated thrombotic phenotypes remain incompletely defined. A panel of 20 cytokines, chemokines and endothelial activation markers was analysed in 37 PAPS patients on stable anticoagulation and 12 healthy controls (HC). We compared concentrations between groups and performed unsupervised hierarchical clustering and principal component analysis (PCA) to identify inflammatory subgroups. Compared with HC, patients with PAPS exhibited significantly elevated levels of 14/20 analytes: granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interferon (IFN)‐γ, interleukin (IL)‐1α, IL‐1β, IL‐6, IL‐10, IL‐12p70, IL‐13, IL‐17a, tumour necrosis factor‐α (TNF‐α), intercellular adhesion molecule‐1 (ICAM‐1), P‐selectin and macrophage inflammatory protein‐1β (MIP1β) (all p < 0.05). Unsupervised clustering identified three inflammatory antiphospholipid syndrome (APS) subgroups distinct from HC. A core cytokine signature comprising GM‐CSF, IL‐6, IL‐10, IL‐12p70, IL‐13 and TNF‐α was elevated across all APS clusters. One cluster, enriched for arterial thrombosis, demonstrated a more pronounced inflammatory phenotype, with increased IFN‐α. Comparison of phenotypes showed significantly higher concentrations of GM‐CSF, IFN‐α, IL‐1α, IL‐4, IL‐6, IL‐10, IL‐17a and TNF‐α in arterial versus venous thrombosis. Our findings demonstrate widespread cytokine dysregulation and distinct inflammatory subgroups in PAPS, with arterial thrombosis showing stronger inflammation than venous thrombosis, supporting divergent thrombo‐inflammatory mechanisms and potential precision immunomodulatory therapeutic targets.
SN - 0007-1048
SN - 1365-2141
ER -