Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs

• DOI: 10.1016/j.biopha.2024.116357
• Publication Date: 2024-03-12T22:55:14Z
• Authors: Laura Muñoz-Barrera; Carlos Perez-Sanchez; Rafaela Ortega-Ca...; Sagrario Corrales; Maria Luque-Tevar; Tomás Cerdó; Ismael Sanchez-Pa...; Pilar Font; Raquel Lopez-Mejías; Jerusalem Calvo; M.Carmen Abalos-A...; Desiree Ruiz-Vilchez; Pedro Segui; Christian Merlo; José Perez-Venegas; Ma Dolores Ruiz M...; Carlos Rodriguez-...; Carmen Romero Barco; Antonio Fernandez...; Natalia Mena Vazque; Jose Luis Marenco; Julia Uceda Montañes; Javier Godoy-Nava...; Alba Ma Cabezas-L...; Eduardo Collantes...; Ma Angeles Aguirre; Miguel A. Gonzále...; Nuria Barbarroja; Alejandro Escuder...; Chary Lopez-Pedrera
• Keywords: 03 medical and health sciences; 0302 clinical medicine

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 ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; 3) characterize molecular mechanisms in immune-cell activation endothelial dysfunction. A total 387 RA patients 45 healthy donors were recruited, forming three cohorts: i) 208 established disease but without previous CV events; ii) RA-CVD: 96 events, iii) 83 treated b-DMARDs/ts-DMARDs for 6 months. Serum profiles (cytokines/chemokines/growth factors) NETosis/oxidative stress-linked biomolecules evaluated. Mechanistic vitro studies performed on monocytes, neutrophils cells (EC). In first RA-cohort, unsupervised clustering unveiled distinct groups: cluster 3 (C3) displayed highest profile, significant CV-risk score, greater atheroma plaques prevalence. contrast, 1 (C1) exhibited lowest risk while 2 (C2) an intermediate phenotype. Notably, 2nd cohort RA-CVD mirrored C3's inflammation. Treatment b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) restored normal levels, controlling risk. vitro, serum from C3-RA increased activity CV-related protein levels cultured monocytes EC, which partially prevented by pre-incubation JAKinibs. Overall, analyzing circulating holds potential personalized management, addressing assisting healthcare professionals tailoring treatment, ultimately improving outcomes.