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Thromb Haemost
DOI: 10.1055/a-2467-6826
Blood Cells, Inflammation, and Infection

Circulating Levels of Low-Density Granulocytes and Cell-Free DNA as Predictors of Cardiovascular Disease and Bone Deterioration in SLE Patients

Ana Suárez   *
1   Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain
2   Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
,
Uxía Tobío-Parada   *
1   Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain
2   Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
,
Javier Rodríguez-Carrio
1   Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain
2   Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
,
Aleida Martínez-Zapico   **
3   Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain
4   Department of Neurology, Hospital Universitario Central de Asturias, Oviedo, Spain
,
Ángel I. Pérez-Álvarez
2   Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
4   Department of Neurology, Hospital Universitario Central de Asturias, Oviedo, Spain
,
Silvia Suárez-Díaz
2   Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
3   Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain
,
Luis Caminal-Montero
2   Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
3   Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain
,
Patricia López
1   Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain
2   Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
› Author Affiliations
Funding This work was supported by the Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación, FEDER-Una manera de hacer Europa (PID2021–122391OB-I00) and Fondo de Investigación Sanitaria (FIS PI16/00113).
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Abstract

Objective The present work evaluates the predictive value of low-density granulocytes (LDGs) for the development of cardiovascular disease (CVD) and/or bone deterioration (BD) in a 6-year prospective study in systemic lupus erythematosus (SLE). Considering the high SLE-LDG capacity to form neutrophil extracellular traps (NETs), circulating levels of total cell-free DNA (cirDNA) and relative amounts of mitochondrial and nuclear DNA (mtDNA and nDNA, respectively) were tested as LDG-associated biomarkers to identify SLE patients at risk of CVD and BD.

Material and Methods The frequency of total blood LDGs, as well as the CD16negCD14neg (nLDG) and CD16posCD14low (pLDG) subsets, was quantified by flow cytometry in 33 controls and 144 SLE patients. Total cirDNA and relative amounts of mitochondrial (mtDNA) and nuclear (nDNA) cell-free DNA were measured by fluorometry or qPCR in plasma from a subgroup of 117 patients and 23 controls at enrolment.

Results and Conclusion Our findings showed increased blood levels of SLE-nLDGs at enrolment associated with prospective CVD development (pCVD) and the presence of BD, thus revealing LDG expansion as a predictor of both comorbidities in SLE progression. The amounts of the different types of circulating DNA analyzed were increased in patients, especially those presenting with traditional CV risk factors or subclinical atheromatosis. Similar to nLDGs, the nDNA concentration could predict the development of pCVD in SLE, supporting the quantification of cirDNA levels as a surrogate marker of LDGs in clinical practice.

Keywords

low-density granulocytes (LDGs) - circulating cell-free DNA (cirDNA) - cardiovascular disease (CVD) - bone loss - systemic lupus erythematosus (SLE)

* These authors are co-first authors.


** Present address of Aleida Martínez-Zapico: Department of Internal Medicine, Hospital Universitario de Cabueñes, Gijón, Spain


Supplementary Material



Publication History

Received: 28 May 2024

Accepted: 13 November 2024

Accepted Manuscript online:
14 November 2024

Article published online:
18 December 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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