Biomarkers Predictive of Ultrasound-detected Arthritis

Researchers for the Risk RA Prospective Study presented the results of their analysis in a presentation at the American College of Rheumatology/Empowering Rheumatology Professionals Annual Meeting.

“Studies have shown that anti-citrullinated protein antibodies (ACPA) are a risk factor for the development of arthritis,” the authors wrote in their abstract. “We aimed to investigate in a prospective setting whether ACPA and other biomarkers could predict the development of ultrasound detected arthritis.”

The study included patients with positive ACPA test who did not have arthritis in the feet, hands, or any other symptomatic joints. Patients underwent a clinical examination and bloodwork that was analyzed for 13 specific ACPA reactivities and 92 inflammation-associated protein biomarkers. DR low-resolution kit was used to determine HLA-SE presence. Analyses were conducted to evaluate the correlation between clinical and laboratory parameters and development of ultrasound-detected arthritis.

During a median follow-up of 11 months, 46% (n=30/65) of the Risk RA patients developed ultrasound-detectable arthritis. The other 54% (n=35/55) were followed for a median 27 months and did not present any signs of ultrasound-detectable arthritis. The patients who developed arthritis, compared to those who did not, had a higher prevalence of HLA-SE (83 percent vs. 55%) and ultrasound-detected tenosynovitis (40% vs. 5%). Patients who developed ultrasound-detectable arthritis had higher rates of ACPA reactivities to citrullinated vimentim peptides (cit vim 2–17: 20% vs. 6%; cit vim 60–75: 67% vs. 44%) and citrullinated histone peptides (cit H4 31–50: 87% vs. 47%; cit H3 21–44: 47% vs. 22%). Upon backward selection in a Cox regression model, ultrasound-detectable arthritis was predictable using a model including HLA-SE, tenosynovitis, and ACPA reactivity to cit H4 31–50. HLA-SE carriers were more likely to develop arthritis (hazard ratio [HR]=2.2, 95% CI; 0.8 to 6.0, P=0.13), as were patients with tenosynovitis (HR=2.9, 95% CI; 1.3 to 6.5, P=0.01) and Anti-citrullinated H4 31-50 positivity (HR=3.4, 95% CI; 1.2 to 10.0, P=0.02). The study authors reported “modest differences” for few of the inflammatory markers tested in patients who developed ultrasound-detectable arthritis versus patients who did not: Interleukin-6 (3.9 vs. 3.3 AU/ML), Programmed death-ligand 1 (4.9 vs. 5.2 AU/ML) and Chemokine (C-X-C motif) ligand 6 (9.2 vs. 9.5 AU/ML).