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Integrative Multiomics Approaches Identify Biomarkers Associated With Progression From Arthralgia to Rheumatoid

Min Li1,2, Yipeng Han1, Minghua Zhan3,4

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This summary is machine-generated.

Immune dysregulation, particularly reduced regulatory T cells (Tregs) and Treg/Th17 ratio, characterizes arthralgia progressing to rheumatoid arthritis (RA). This Treg imbalance may drive the transition to persistent inflammatory arthritis.

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Area of Science:

  • Rheumatology
  • Immunology
  • Translational Medicine

Background:

  • Arthralgia precedes rheumatoid arthritis (RA) and is a key window for early intervention.
  • Understanding the immunopathology of arthralgia progression to RA is crucial but incomplete.

Purpose of the Study:

  • To investigate the immunopathological continuum from preclinical arthralgia to established RA using a multi-omics approach.
  • To identify biomarkers predicting RA development in individuals with arthralgia.

Main Methods:

  • A prospective cohort of 346 patients with recent-onset arthralgia underwent immune cell phenotyping, serum proteomics, and autoantibody profiling.
  • Patients were categorized into healthy controls, self-limiting arthralgia (SLA), arthralgia at risk of RA (ARI), early RA, and established RA.
  • RA development in ARI was monitored over 24 months.

Main Results:

  • Arthralgia at risk of RA (ARI) exhibited immune dysregulation, including reduced regulatory T cells (Tregs) and a lower Treg/Th17 ratio, persisting into early RA.
  • Serum proteomics identified specific protein upregulations (C5, A1BG, RPUSD4, WDR87, FUBP2) inversely associated with Tregs.
  • The Treg/Th17 ratio showed superior discrimination of ARI from SLA compared to anti-CCP, especially in ACPA-negative patients.

Conclusions:

  • A transition from reversible immune dysregulation to established autoimmunity occurs along the arthralgia-RA continuum.
  • Treg-related dysregulation is associated with progression toward persistent inflammatory arthritis.
  • Combined biomarkers including Tregs, anti-CCP, and Treg/Th17 ratio improve RA prediction.