Novel Biomarker Test Distinguishes RA From OA

van Schaardenburg D, Murphy M, Gui Y, et al. Change in 14-3-3n Expression in Early RA Patients Treated with DMARDS Corresponds with Change in DAS 28 and Good EULAR ResponsesArthritis & Rheumatism. 2014. 66(1). ACR Abstract #1903

Wichuk S, Lambert RG, Murphy M et al.Autoantibodies to 14-3-3n are novel biomarkers associated with Inflammation and Radiographic Progression in Ankylosing Spondylitis Arthritis & Rheumatism. 2014. 66(1). Supplement. ACR Abstract #2985

Rheumatoid arthritis (RA) and osteoarthritis (OA) both cause joint pain and morning stiffness. Early in the disease process, it’s often hard to tell one from the other during a clinical exam. But now a simple blood test can.

It’s a soluble biomarker for a pro-inflammatory mediator called 14-3-3eta that is elevated in the blood of RA patients but virtually non-existent in people with OA.

“The protein discriminates quite nicely between RA and OA. The specificity of marker is in the 90% range for RA, both early and established, but it is not found or titers are small in people with OA,” explains Anthony Marotta, PhD, chief scientific officer or Augurex Life Sciences in Vancouver, who developed the test with Walter Maksymowych MD, professor of rheumatology at the University of Alberta, and others.

In a just-published study of in the Journal of Rheumatology, Maksymowych and co-authors report that 14-3-3eta was seven-fold higher in patients with established RA (n=135) and six times higher in early RA (n=99), while being almost non-existent in OA (n=30), compared to disease controls and healthy people.

“It will not only help tease apart RA and OA, but we also hope it will become a complementary assay to help with the diagnosis of RA,” Marotta told Rheumatology Network in an interview.

Concentrations of 14-3-3eta are also significantly higher in people with active RA than in those with inactive disease, van Schaardenburg told an ACR session on promising biomarkers.  

“We’re now running pre-clinical animal studies to determine whether treatment has any effects on 4-3-3eta. So in the future, the markers could not only inform who to treat and but how to treat,” Marotta adds.

High titers of 14-3-3eta indicate more severe disease activity in RA, while low titers of the biomarker may indicate a good response to anti-tumor necrosis-alpha (TNFα) drugs, Maksymowych told the European League Against Rheumatism (EULAR) annual meeting in June.

In the RAPPORT trial, among 75 patients with established RA who were given anti-TNFα therapy, the 20% who achieved a good EULAR response at 15 weeks post-treatment had significantly lower median serum 14-3-3eta at baseline (0.72 ng/ml) compared to those with lesser responses (2.52 ng/ml).

The biomarker is also associated with inflammation and radiographic progression in AS, Maksymowych told the audience at the ACR meeting in Boston. The biomarker was prominently featured at other ACR sessions, with over 14 abstracts and podium presentations.

An assay for 14-3-3eta is available in the US as a CLIA-approved, laboratory-developed test from Quest Diagnostics.