ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2244

Unveiling Synovial Protein Contributions to Serum Inflammation, Disease Activity, and Treatment Outcomes in RA Patients

Chary Lopez-Pedrera1, Sagrario Corrales2, Julio Osuna3, Rafaela Ortega-Castro4, Jerusalén Calvo3, María Lourdes Ladehesa-Pineda1, Ismael Sánchez Pareja2, Laura Muñoz-Barrera2, Desiree Ruiz-Vilchez3, Christian Merlo5, Mª Angeles Aguirre-Zamorano6, Nuria Barbarroja2, Tomás Cerdó2, Rosa ortega3, Marta Alarcon-Riquelme7, Carlos Perez-Sanchez2, Alejandro Escudero-Contreras2 and Concepción Aranda-Valera8, 1IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Andalucia, Spain, 2IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, 3IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Spain, 4Hospital Reina Sofía, Cordoba, Andalucia, Spain, 5Rheumatology Service, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain, 6IMIBIC/Reina Sofia Hospital/University of Cordoba, CÓRDOBA, Andalucia, Spain, 7Fundación Progreso y Salud, Andalusian Government, Granada, Spain, 8IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Andalucia, Spain

Meeting: ACR Convergence 2024

Keywords: , , ,

Session Information

Date: Monday, November 18, 2024

Title: RA – Diagnosis, Manifestations, & Outcomes Poster III

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose:

  1. Characterize synovial tissue-secreted proteins in RA patients that contibute to serum inflammatory profiles based on immune cell infiltration.
  2. Identify RA patient subsets with distinctive serum levels of these proteins, their correlation with disease activity, and early clinical response to conventional DMARDs.

Methods: Histomorphological features of synovial explants obtained via ultrasound (US)-guided biopsies of 17 early RA patients were analyzed, including lining thickness, inflammation, fibrosis, and immune cell infiltration (T and B lymphocytes, plasma cells, and macrophages identified with anti-CD3, anti-CD20, anti-CD138, and anti-CD68 antibodies). These tissues were cultured in vitro for 24 hours to profile secreted proteins using proximity extension assay (PEA) technology (Olink) for 92 inflammation-related proteins. This proteomic profile was also analyzed in serum samples from the same subjects and correlation studies were conducted. Relevant signatures were tested in an independent cohort of 83 early-stage RA patients, evaluating their association with response to conventional DMARDs.

Results: Histopathological analysis revealed a predominance of lymphohistiocytic inflammation in RA synovium with abundant CD3+ and CD68+ infiltrated cells, associated with increased lining thickness, inflammation, and fibrosis.
Ten synovial-secreted proteins (CDCP1, CXCL1, IL10RA, IL10RB, IL10, IL15RA, PDL1, CCL28, IFN-gamma, FGF19) correlated with serum levels in RA patients. Elevated levels were observed in patients with active disease (DAS28 > 3.2), increased acute phase reactants (APR), and ACPAs positivity. Significant correlations existed between synovial-secreted protein levels and enhanced synovial CD3+ T-lymphocyte infiltration, suggesting immune infiltration as the protein source.
In an independent cohort of 83 early-stage RA patients treated with conventional DMARDs, serum levels of this ten-protein signature were evaluated. Unsupervised clustering identified two patient groups with distinct protein profiles. The group with higher inflammatory signature levels exhibited higher disease activity and better response to conventional DMARDs after three months.

Conclusion: We identified a ten-protein signature secreted by the synovial tissue contributing to the circulating inflammatory profile in RA patients. These proteins were closely linked to immune infiltration in the synovium and correlated with clinical features and early response to conventional DMARDs.
This study highlights the potential for personalized RA treatment selection using biomarkers that reflect the molecular characteristics of synovial tissue.

Supported by EU/EFPIA IMI-JU 3TR, ISCIII (PI21/0591, CD21/00187 and RICOR-21/0002/0033), co-financed by European Union, and MINECO (RYC2021-033828-I/PID2022-141500OA-I00).

Disclosures: C. Lopez-Pedrera: Eli Lilly, 5; S. Corrales: None; J. Osuna: None; R. Ortega-Castro: None; J. Calvo: None; M. Ladehesa-Pineda: None; I. Sánchez Pareja: None; L. Muñoz-Barrera: None; D. Ruiz-Vilchez: None; C. Merlo: None; M. Aguirre-Zamorano: None; N. Barbarroja: None; T. Cerdó: None; R. ortega: None; M. Alarcon-Riquelme: None; C. Perez-Sanchez: None; A. Escudero-Contreras: None; C. Aranda-Valera: None.

To cite this abstract in AMA style:

Lopez-Pedrera C, Corrales S, Osuna J, Ortega-Castro R, Calvo J, Ladehesa-Pineda M, Sánchez Pareja I, Muñoz-Barrera L, Ruiz-Vilchez D, Merlo C, Aguirre-Zamorano M, Barbarroja N, Cerdó T, ortega R, Alarcon-Riquelme M, Perez-Sanchez C, Escudero-Contreras A, Aranda-Valera C. Unveiling Synovial Protein Contributions to Serum Inflammation, Disease Activity, and Treatment Outcomes in RA Patients [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/unveiling-synovial-protein-contributions-to-serum-inflammation-disease-activity-and-treatment-outcomes-in-ra-patients/. Accessed .

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