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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1374100

Circulating extracellular vesicles as novel biomarkers for pulmonary arterial hypertension in patients with systemic lupus erythematosus

Provisionally accepted
Zhe Ding Zhe Ding 1,2Fumin Qi Fumin Qi 1,2*Li Liu Li Liu 3*Zhouming Wang Zhouming Wang 4*Na Zhang Na Zhang 1,2*Xing Lyu Xing Lyu 1,2*Wenwen Sun Wenwen Sun 1,2*Jun Du Jun Du 1,2*Haoming Song Haoming Song 5*Hou Hou Hou Hou 1,2*Ying Guo Ying Guo 1,2*Xiaomei Wang Xiaomei Wang 1,2*Ming-Lin Liu Ming-Lin Liu 6,7*Wei Wei Wei Wei 1,2*
  • 1 Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
  • 2 Tianjin Clinical Research Center for Rheumatic and Immune Diseases, Tianjin, China
  • 3 Institute of Neurology, Tianjin Medical University General Hospital, Tianjin, China
  • 4 Department of Cardiovascular Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China
  • 5 Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
  • 6 Corporal Michael J. Crescenz VA Medical Center, United States Department of Veterans Affairs, Philadelphia, United States
  • 7 Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States

The final, formatted version of the article will be published soon.

    Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with increased mortality. A prothrombotic state may contribute to pathogenesis of SLE-PAH. Extracellular vesicles (EVs) are known to be associated with thrombosis. Here, we investigated circulating EVs and their associations with SLE-PAH. Eighteen SLE-PAH patients, 36 SLE-non-PAH patients, and 36 healthy controls (HCs) were enrolled. Flow cytometry was used to analyze circulating EVs from leukocytes (LEVs), red blood cells (REVs), platelets (PEVs), endothelial cells (EEVs), and Annexin V+ EVs with membrane phosphatidylserine (PS) exposure. Plasma levels of all EV subgroups were elevated in SLE patients with or without PAH compared to HCs. Furthermore, plasma Annexin V+ EVs, LEVs, PEVs, REVs, EEVs, and Annexin V+ REVs were significantly elevated in SLE-PAH patients compared to SLE-non-PAH patients. Additionally, PAH patients with moderate/high SLE showed a significant increase in LEVs, PEVs, REVs, Annexin V+ EVs, and Annexin V+ REVs compared to SLE-non-PAH patients. However, PAH patients with inactive/mild SLE only exhibited elevations in Annexin V+ EVs, REVs, and Annexin V+ REVs. In the SLE-PAH patients, EEVs were positively correlated with pulmonary arterial systolic pressure, while PEVs and EEVs were positively correlated with right ventricular diameter. Moreover, the receiver operating characteristic curve indicated that Annexin V+ EVs, LEVs, PEVs, REVs, EEVs and Annexin V+ REVs could predict the presence of PAH in SLE patients. Importantly, multivariate logistic regression analysis showed that circulating levels of LEVs or REVs, anti-nRNP antibody, and serositis were independent risk factors for PAH in SLE patients. In conclusion, our findings reveal that specific subgroups of circulating EVs contribute to the hypercoagulation state and the severity of SLE-PAH. Higher plasma levels of LEVs or REVs may serve as biomarkers for SLE-PAH.

    Keywords: Systemic lupus erythematosus2, Pulmonary arterial hypertension3, Biomarker4, Procoagulant5, Extracellular vesicles1

    Received: 21 Jan 2024; Accepted: 28 Aug 2024.

    Copyright: © 2024 Ding, Qi, Liu, Wang, Zhang, Lyu, Sun, Du, Song, Hou, Guo, Wang, Liu and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Fumin Qi, Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
    Li Liu, Institute of Neurology, Tianjin Medical University General Hospital, Tianjin, China
    Zhouming Wang, Department of Cardiovascular Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China
    Na Zhang, Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
    Xing Lyu, Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
    Wenwen Sun, Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
    Jun Du, Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
    Haoming Song, Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
    Hou Hou, Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
    Ying Guo, Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
    Xiaomei Wang, Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
    Ming-Lin Liu, Corporal Michael J. Crescenz VA Medical Center, United States Department of Veterans Affairs, Philadelphia, United States
    Wei Wei, Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.