Active Rheumatoid Arthritis Patients Exhibit an Altered Serum Lipidomic Profile Directly Linked to Disease Activity, Which Is Reversed by Biologic and Targeted Synthetic DMARD

Chary Lopez-Pedrera¹, Laura Muñoz-Barrera², Beatriz Vellón², Rocio Guzman², Tomás Cerdó², Rafaela Ortega Castro³, Jerusalem Calvo⁴, Mª Angeles Aguirre⁵, Pedro Segui², Ivan Arias de la Rosa⁶, Maria del Carmen Abalos-Aguilera⁷, Desiree Ruiz-Vilchez², Christian Merlo-Ruiz², Jose Javier Perez-Venegas⁸, Javier Godoy⁹, Dolores Ruiz-Montesinos¹⁰, Carmen Dominguez⁸, Carlos Rodriguez-Escalera¹¹, Carmen Romero-Barco¹², Antonio Fernandez-Nebro¹², Natalia Mena Vazquez¹³, Julia Uceda Montañez¹⁴, Charo Santos¹⁴, Nuria Barbarroja¹⁵, Eduardo Collantes Estévez¹⁶, Mª del Mar Malagon², Alejandro Escudero Contreras⁴ and Carlos Perez-Sanchez¹⁷, ¹IMIBIC - Reina Sofia Hospital, Córdoba, Spain, ²IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Spain, ³Hospital Reina Sofía, Cordoba, Spain, ⁴Reina Sofia University Hospital, Córdoba, Spain, ⁵Reina Sofía University Hospital/ Rheumatology Department, Córdoba, Spain, ⁶IMIBIC/Reina Sofia Hospital/University of Cordoba. Rheumatology service. Cordoba. Spain, Cordoba, Spain, ⁷Rheumatology Department, Reina Sofia University Hospital/Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain, ⁸Virgen Macarena University Hospital, Sevilla, Spain, ⁹Jaen University Hospital, Jaen, Spain, ¹⁰Hospital Universitario Virgen Macarena, Sevilla, Spain, ¹¹Virgen de la Victoria Hospital, Malaga, Spain, ¹²Hospital Regional Universitario de Málaga, Malaga, Spain, ¹³IBIMA, Málaga, Spain, ¹⁴Hospital Virgen de Valme, Sevilla, Spain, ¹⁵University of Cordoba, Córdoba, Spain, ¹⁶Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba, Cordoba, Spain, ¹⁷IMIBIC, Córdoba, Spain

Meeting: ACR Convergence 2023

Keywords: Disease Activity, Disease-Modifying Antirheumatic Drugs (Dmards), metabolomics, rheumatoid arthritis

Session Information

Date: Monday, November 13, 2023

Title: (1264–1307) RA – Diagnosis, Manifestations, and Outcomes Poster II

Session Type: Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Lipid metabolism impacts immune cell plasticity, activation, differentiation, and function, making the analysis of the lipidomic profile crucial in understanding chronic inflammatory diseases like Rheumatoid Arthritis (RA). High throughput metabolomic techniques offer a comprehensive view of lipid metabolism and can contribute to characterizing the pathogenesis of RA.
This study aimed to analyze the lipidomic profile in the serum of RA patients, examine its association with disease activity, and investigate how biological and targeted synthetic therapies modulate this profile.

Methods: A total of 250 consecutive RA patients participated, providing serum samples and clinical data (disease activity, acute phase reactants, autoimmune profile). Nightingale LTD’s nuclear magnetic resonance (NMR) spectroscopy, covering over 200 lipid markers, was used to analyze the lipidomic profile. Additionally, a subgroup of active RA patients underwent prospective monitoring after receiving biologics (anti-TNF: n=50, anti-IL6R: n=15) or JAK inhibitors (JAKi: n=20). Serum samples collected before and after therapy evaluated changes in the lipid and clinical profiles. In vitro studies using an oil red staining assay examined lipid accumulation in HepG2 liver cells treated with serum from RA patients with varying disease activity.

Results: RA patients were divided into high (68), moderate (117), and low (65) disease activity groups. Approximately 100 lipid markers showed significant alterations across these groups. Interestingly, patients with high disease activity exhibited reduced levels of numerous lipid markers, including apolipoproteins, cholesterol, fatty acids (SFA, MUFA, PUFA, Omega 3 and 6, LA, DHA), triglycerides, cholines, phospholipids, lipoproteins (HDL, LDL, VLDL), and total lipid content in lipoproteins. Strong correlations were found between these lipid markers and inflammatory (CRP, ESR) and autoimmune parameters (ACPAs, RF). After six months of therapy, lipid markers significantly increased alongside clinical and analytical improvements in RA patients. Each drug demonstrated both common and distinct molecules that reversed the altered lipid metabolism. In vitro studies showed lipid accumulation in HepG2 liver cells treated with serum from RA patients with high disease activity compared to those with low disease activity, suggesting inflammation-induced altered hepatocyte metabolism as a potential contributor to reduced circulating lipid profiles.

Conclusion: Active RA patients exhibit a significantly reduced lipidomic profile directly linked to disease activity, inflammatory markers, and autoimmune parameters. Biological therapies and JAK inhibitors restore the altered lipid metabolism concurrently with clinical improvement. In vitro studies support the hypothesis that inflammation-induced lipid accumulation in the liver may partially explain the reduction in circulating lipid profiles in active patients. Ongoing studies aim to uncover the underlying mechanisms of these effects. Supported by ISCIII (PI21/0591, CD21/00187, RD21/0002/0033), RYC2021-033828-I, J. Andalucía (P20_01367) co-financed by FEDER; Fundacion Andaluza de Reumatología.

Disclosures: C. Lopez-Pedrera: None; L. Muñoz-Barrera: None; B. Vellón: None; R. Guzman: None; T. Cerdó: None; R. Ortega Castro: None; J. Calvo: None; M. Aguirre: None; P. Segui: None; I. Arias de la Rosa: None; M. Abalos-Aguilera: None; D. Ruiz-Vilchez: None; C. Merlo-Ruiz: None; J. Perez-Venegas: None; J. Godoy: None; D. Ruiz-Montesinos: None; C. Dominguez: None; C. Rodriguez-Escalera: None; C. Romero-Barco: None; A. Fernandez-Nebro: None; N. Mena Vazquez: None; J. Uceda Montañez: None; C. Santos: None; N. Barbarroja: None; E. Collantes Estévez: None; M. Malagon: None; A. Escudero Contreras: None; C. Perez-Sanchez: None.

To cite this abstract in AMA style:

Lopez-Pedrera C, Muñoz-Barrera L, Vellón B, Guzman R, Cerdó T, Ortega Castro R, Calvo J, Aguirre M, Segui P, Arias de la Rosa I, Abalos-Aguilera M, Ruiz-Vilchez D, Merlo-Ruiz C, Perez-Venegas J, Godoy J, Ruiz-Montesinos D, Dominguez C, Rodriguez-Escalera C, Romero-Barco C, Fernandez-Nebro A, Mena Vazquez N, Uceda Montañez J, Santos C, Barbarroja N, Collantes Estévez E, Malagon M, Escudero Contreras A, Perez-Sanchez C. Active Rheumatoid Arthritis Patients Exhibit an Altered Serum Lipidomic Profile Directly Linked to Disease Activity, Which Is Reversed by Biologic and Targeted Synthetic DMARD [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/active-rheumatoid-arthritis-patients-exhibit-an-altered-serum-lipidomic-profile-directly-linked-to-disease-activity-which-is-reversed-by-biologic-and-targeted-synthetic-dmard/. Accessed .

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