Serum Proteomic Signatures of Rheumatoid Arthritis Risk and Response: Analysis of a Rheumatoid Arthritis Interception...

Area of Science:

• Immunology
• Biochemistry
• Rheumatology

Background:

• Rheumatoid arthritis (RA) poses a significant health burden.
• Identifying early biomarkers for RA progression and treatment response is crucial for effective management.
• Understanding the immune landscape in the pre-RA phase can inform preventative strategies.

Purpose of the Study:

• To identify serum protein signatures associated with progression to rheumatoid arthritis (RA).
• To determine protein signatures linked to treatment response with abatacept in at-risk individuals.
• To explore the immune landscape during the at-risk phase of RA.

Main Methods:

• Analysis of 440 serum samples from 118 participants in the APIPPRA study.
• Utilized the SomaScan® 7k assay platform for comprehensive protein analysis.
• Differential expression analysis was performed based on RA progression and treatment allocation (abatacept vs. placebo).

Main Results:

• Identified 80 proteins with significant changes preceding RA onset (6-24 months prior).
• Progression to RA was associated with increased acute phase reactants (SAA1, SAA2) and decreased CTLA4.
• Abatacept treatment was linked to changes in specific proteins including CTLA4, CD86, CXCL13, and others, irrespective of RA outcome.

Conclusions:

• Serum protein signatures, particularly acute phase proteins, effectively define RA progression.
• Abatacept therapy-associated protein changes offer insights into treatment response mechanisms.
• These signatures enhance understanding of the pre-RA immune environment, potentially guiding new RA prevention strategies.