Plasma Protein Fluctuation Trajectories Over 15 Years Before Rheumatoid Arthritis Onset.

Area of Science:

• Biochemistry
• Immunology
• Genomics

Background:

• Rheumatoid arthritis (RA) leads to significant long-term disability and patient distress.
• The early pathogenesis and dynamic changes preceding RA onset are not fully understood.

Purpose of the Study:

• To investigate associations between plasma proteins and incident RA.
• To characterize protein fluctuation patterns in the 15 years prior to RA development.

Main Methods:

• Analysis of 2923 plasma proteins in the UK Biobank cohort with a 15-year follow-up.
• Identification of proteins associated with RA risk and examination of their temporal changes.
• Development and validation of predictive models for RA onset.

Main Results:

• 460 significant protein-RA associations were identified, primarily involving immune responses.
• 26 proteins showed significant fluctuations over 15 years before RA onset, including IL6 and IFI30.
• A predictive model using these proteins achieved high AUC values (0.818 training, 0.766 testing), further improved with demographic data (0.871 training, 0.919 testing).

Conclusions:

• Plasma protein profiles change dynamically over 15 years preceding RA onset.
• These protein fluctuations provide valuable insights into early RA pathogenesis.
• Proteins like IL6, IFI30, CDCP1, TGFA, GDF15, and EDA2R are key indicators of early RA risk.