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Abstract Number: 0879

Anti-dsDNA Antibodies Increase Systemic Lupus Erythematosus Cardiovascular Risk Impairing the Immune and Cardiovascular Systems

Carlos Pérez-Sánchez1, Alejandra Patiño-Trives2, Maria Angeles Aguirre3, Laura Perez-Sanchez3, Chary Lopez-Pedrera3, Maria Luque-Tevar2, Maria del Carmen Ábalos-Aguilera3, Iván Arias de la Rosa4, Cristobal Román-Rodriguez3, Pedro Segui3, Mario Espinosa3, Pilar Font3, Nuria Barbarroja4, alejandro Escudero3, Eduardo Collantes-Estevez3, Jose Antonio Gonzalez-Reyes5, Jose Manuel Villalba5 and Chary lopez-pedrera3, 1IMIBIC, Córdoba, Spain, 2Rheumatology Department, Reina Sofia University Hospital/ Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ University of Cordoba, Cordoba, Spain, 3IMIBIC/Reina Sofia Hospital/University of Córdoba, Córdoba, Spain, 4University of Cordoba/IMIBIC/Reina Sofia Hospital, Cordoba, Spain, 5Department of Cell Biology, Physiology and Immunology, University of Córdoba, Campus de Excelencia Internacional Agroalimentario, ceiA3, Cordoba, Spain

Meeting: ACR Convergence 2021

Keywords: anti-dsDNA, Cardiovascular, Gene Expression, Proteome, Systemic lupus erythematosus (SLE)

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Session Information

Date: Sunday, November 7, 2021

Title: SLE – Diagnosis, Manifestations, & Outcomes Poster II: Manifestations (0855–0896)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: This study aimed to delineate the role of anti-dsDNA antibodies on the alterations observed in the gene profile and the activity of immune and vascular cells in systemic lupus erythematosus (SLE) patients, as well as on their cardiovascular risk.

Methods: Eighty SLE patients were included. Extensive clinical/analytical evaluation was performed, including parameters related to cardiovascular diseases (CVD) such as endothelial function, proatherogenic dyslipidemia, and carotid intima-media thickness. Gene and protein expression profiles were evaluated in monocytes from patients positive and negative for anti-dsDNA antibodies by using Nanostring and cytokine arrays respectively. NETosis was assessed in both, neutrophils and plasma through analysis of nucleosomes, neutrophil elastase, and myeloperoxidase. The circulating inflammatory profile was also quantified by Luminex assays.

Results: Positivity and persistence of anti-dsDNA antibodies in SLE patients were found associated with endothelial dysfunction, pro-atherogenic dyslipidemia, and accelerated atherosclerotic process. In parallel, anti-dsDNA antibodies were linked to the aberrant activation of innate immune cells, so that anti-dsDNA(+) SLE monocytes showed distinctive gene and protein expression/activity profiles, and neutrophils were more prone to suffer NETosis in comparison with anti-dsDNA(-) patients. Anti-dsDNA(+) patients further displayed altered levels of numerous circulating mediators related to inflammation, NETosis, and enhanced CV risk. In vitro, Ig-dsDNA promoted NETosis on neutrophils, apoptosis on monocytes, modulated the expression of inflammation and thrombosis-related molecules, and induced endothelial activation, at least partially, by FcR-binding mechanisms.

Conclusion: Anti-dsDNA antibodies increase the cardiovascular risk of SLE patients by altering key molecular features that drive a distinctive and coordinated immune and vascular activation.
Funded by ISCIII, PI18/00837 and RIER RD16/0012/0015 co-funded with FEDER


Disclosures: C. Pérez-Sánchez, None; A. Patiño-Trives, None; M. Aguirre, None; L. Perez-Sanchez, None; C. Lopez-Pedrera, None; M. Luque-Tevar, None; M. Ábalos-Aguilera, None; I. Arias de la Rosa, None; C. Román-Rodriguez, None; P. Segui, None; M. Espinosa, None; P. Font, None; N. Barbarroja, None; a. Escudero, None; E. Collantes-Estevez, None; J. Gonzalez-Reyes, None; J. Villalba, None; C. lopez-pedrera, None.

To cite this abstract in AMA style:

Pérez-Sánchez C, Patiño-Trives A, Aguirre M, Perez-Sanchez L, Lopez-Pedrera C, Luque-Tevar M, Ábalos-Aguilera M, Arias de la Rosa I, Román-Rodriguez C, Segui P, Espinosa M, Font P, Barbarroja N, Escudero a, Collantes-Estevez E, Gonzalez-Reyes J, Villalba J, lopez-pedrera C. Anti-dsDNA Antibodies Increase Systemic Lupus Erythematosus Cardiovascular Risk Impairing the Immune and Cardiovascular Systems [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/anti-dsdna-antibodies-increase-systemic-lupus-erythematosus-cardiovascular-risk-impairing-the-immune-and-cardiovascular-systems/. Accessed .
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