@article{10902/32976,
year = {2024},
url = {https://hdl.handle.net/10902/32976},
abstract = {Background & objectives: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. Patients & methods: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). Results: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation. Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. Conclusions: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.},
organization = {Funding sources This study was supported by grants: PI21/00591 and PI20/00079, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union); ‘RD21/0002/0033’ -Health Outcomes-Oriented Cooperative Research Networks-, granted by the “Instituto de Salud Carlos III (ISCIII)” and “Funded by the European Union – NextGenerationEU”, via “Mecanismo de Recuperacion ´ y Resiliencia (MRR)” and “Plan de Recuperacion, ´ Transformacion ´ y Resiliencia (PRTR)”; Fundacion Andaluza de Reumatología (FAR); Consejería de Conocimiento, Investigacion ´ y Universidad de la Junta de Andalucía (P20_01367); and Ministerio de Ciencia, Innovacion ´ y Universidades (PID2022- 141500OA-I00). CL-P was supported by a contract from the Spanish Junta de Andalucía (‘Nicolas Monardes’ programme). TC was supported by ‘Sara Borrell’ programme of the ISCIII (CD21/00187), LMB was supported by a predoctoral grant from the ISCIII, (FI22/00299). CPS and NBP were financed by a contract from MINECO ‘Ramon y Cajal’ program (RYC2021-033828-I and RyC- 2017-23437), cofounded by the European Union ‘NextGenerationEU’/PRTR.
Acknowledgements: We are grateful to the patients and healthy control donors who participated in this study.},
publisher = {Editions Scientifiques Elsevier},
publisher = {Biomedicine & Pharmacotherapy, 2024, 173, 116357},
title = {Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs},
author = {Muñoz-Barrera, Laura and Pérez-Sánchez, Carlos and Ortega-Castro, Rafaela and Corrales, Sagrario and Luque-Tevar, María and Cerdó, Tomás and Sánchez-Pareja, Isamel and Font, Pilar and López-Mejías, Raquel and Calvo, Jerusalem and Abalos-Aguilera, M. Carmen and Ruiz-Vilchez, Desiree and Segui, Pedro and Merlo, Christian and Pérez-Venegas, José and Ruiz Montesino, M. Dolores and Rodríguez-Escalera, Carlos and Romero Barco, Carmen and González-Gay Mantecón, Miguel Ángel},
}