Researchers Identify 4 Novel Biomarkers to More Accurately Diagnose RA

A 4-biomarker panel can help ensure rheumatoid arthritis (RA) is accurately diagnosed, according to study results published in Arthritis Research & Therapy. Researchers concluded the findings give weight to using the 4 proteins as reliable biomarkers for diagnosing RA.

The panel, consisting of angiotensinogen (AGT), serum amyloid A-4 protein (SAA4), vitamin D-binding protein (VDBP), and retinol-binding protein-4 (RBP4), was found to prevent false negatives throughout the study, which included more than 250 patients with RA and 230 healthy controls.

Traditionally, immunoglobin M (RF) and anti-CCP (ACCP) have served as biomarkers for diagnosis. However, the researchers noted, “Existing biomarkers have limitations concerning RA diagnosis. For example, the sensitivity and specificity of RF are 60-90% and 85%, respectively. To improve the efficiency of RA diagnosis, anti-CCP is used with RF. Anti-CCP has higher ACCP positivity than RF positivity among RA patients; however, the sensitivity and specificity of the 2 markers do not significantly differ.”

In search of novel biomarkers that complement existing ones, investigators tested 7 potential biomarkers by verifying them through multiple reaction monitoring-based quantitative analysis.

From this analysis, researchers observed AGT, SAA4, VDBP, and RBP4 have an area under the curve (AUC) over 0.8, indicating their ability to distinguish between patients with RA and those without the autoimmune disease.

“These 4 biomarker candidates displayed high classification accuracy regardless of the rheumatoid factor (RF)-positive or RF-negative status of patients,” wrote the researchers, who highlighted that AGT accurately classified 83.3% of healthy controls and 73.5% of patients with RA.

In addition, SAA4 accurately classified 88.8% of healthy controls and 76.5% of patients with RA, RBP4 accurately classified 90.8% of healthy controls and 86% of patients with RA, and VDVP accurately classified 90.8% of healthy controls and 86% of patients with RA.

“Together, the 4-biomarker panel accurately classified 234 healthy controls and 210 RA patients with a classification accuracy of 93.2% and 91.7% for healthy controls and RA patients, respectively,” researchers said.

The other 3 biomarker candidates—lymphatic vessel endothelial hyaluronan receptor 1, gelsolin, and C-reactive protein—displayed AUC values of 0.5309, 0.6794, and 0.5030, respectively.

Reference:

Mun S, Lee J, Park M, Shin J, Lim M, Kang H. Serum biomarker panel for the diagnosis of rheumatoid arthritis. Published online January 18, 2021. Arthritis Res Ther. doi:10.1186/s13075-020-02405-7