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  1. Home
  2. Exploring Candidate Biomarkers For Rheumatoid Arthritis Through Cardiovascular And Cardiometabolic Serum Proteome Profiling.
  1. Home
  2. Exploring Candidate Biomarkers For Rheumatoid Arthritis Through Cardiovascular And Cardiometabolic Serum Proteome Profiling.

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Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome

Laura Cuesta-López1, Alejandro Escudero-Contreras1, Yas Hanaee1,2

  • 1Rheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, Spain.

Frontiers in Immunology
|February 29, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Rheumatoid arthritis (RA) patients have increased cardiovascular disease risk. This study identified protein biomarkers for RA and cardiovascular disease, and showed how methotrexate and tofacitinib therapies impact these proteins.

Keywords:
Olinkbiomarkersmethotrexateproximity extension assay (PEA)rheumatoid arthritistofacitinib

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Area of Science:

  • Proteomics
  • Immunology
  • Cardiovascular Medicine

Background:

  • Rheumatoid arthritis (RA) patients face a heightened risk of cardiovascular disease (CVD), often influenced by therapeutic interventions.
  • Understanding the cardiovascular and cardiometabolic proteome in RA is crucial for identifying novel biomarkers and elucidating associated biological pathways.

Purpose of the Study:

  • To identify protein biomarkers associated with cardiovascular disease in rheumatoid arthritis patients.
  • To investigate the impact of methotrexate and tofacitinib therapies on the proteomic profile of RA patients.
  • To explore potential protein markers predictive of treatment response.

Main Methods:

  • Serum protein profiling of 184 proteins using Olink technology in two RA cohorts (newly diagnosed and established disease) and matched healthy donors (HDs).
  • Longitudinal analysis of RA patients treated with methotrexate or tofacitinib for 6 months.
  • Clinical variables, including disease activity score 28 (DAS28), were recorded.
  • Main Results:

    • Elevated levels of 75 proteins were observed in RA patients, potentially linked to CVD. Twenty proteins were commonly altered in both RA cohorts, with CTSL1, SORT1, SAA4, TNFRSF10A, ST6GAL1, and CCL18 discriminating RA from HDs.
    • Methotrexate reduced 13 proteins and tofacitinib modulated 10 proteins, associated with decreased DAS28. SAA4 and BNP levels predicted methotrexate non-response, while IL6 changes indicated response.
    • Treatment response to tofacitinib correlated with baseline LOX1 and CNDP1 levels and changes in SAA4 and TIMD4.

    Conclusions:

    • This study identifies key protein alterations in RA linked to CVD and proposes candidate biomarkers for differentiating RA patients from healthy individuals.
    • Methotrexate and tofacitinib differentially modulate these protein levels, with distinct changes correlating to treatment response.
    • SAA4 emerges as a potential candidate biomarker for predicting response to RA therapies.