Biomarkers in Arthritis: Helping You and Your Doctor See the Full Picture

If you’ve been diagnosed with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA), you know that these conditions can be unpredictable and deeply personal. What works for one person might not work for another, and symptoms, treatment responses, and long-term outcomes can vary widely.

That’s where biomarkers come in. These measurable signals in your blood are becoming a powerful tool to help doctors understand the underlying disease, guide treatment decisions and support more effective disease management.

What Are Biomarkers?

Think of a biomarker as a clue your body leaves behind—something doctors can measure to get insight into disease activity. In arthritis, common biomarkers include:

• Rheumatoid factor (RF)

• Anti-CCP antibodies

• C-reactive protein (CRP)

These are often used to help confirm a diagnosis and monitor inflammation. But newer markers are adding even more insight. One of the most promising is a protein called 14-3-3eta (pronounced “fourteen-three-three-eta”), which has been used in rheumatoid arthritis for over a decade and studied extensively in clinical research.

What Is 14-3-3eta?

14-3-3eta is a protein released by cells in the joints when inflammation is present.1 What makes it different is that it not only reflects inflammation but may also contribute directly to joint damage.1

Because it’s joint-specific, 14-3-3eta gives doctors a more targeted view of what’s happening where arthritis starts. More importantly, it’s helpful not only for diagnosis but also for monitoring disease progression and joint damage risk over time.

In Rheumatoid Arthritis (RA): A Tool for the Long Run

In RA, 14-3-3eta has been studied in thousands of patients—and the results are compelling.

• Elevated 14-3-3eta levels at diagnosis can support earlier detection—especially in patients who test negative for RF or anti-CCP—and are associated with more aggressive disease and a greater risk of joint damage.1,2,3

• Over time, declining levels are generally a good sign indicating treatment is working, while sustained or increasing levels may indicate ongoing joint inflammation or risk of damage.4,5

• It works alongside other markers like RF, anti-CCP, and CRP, giving doctors a clearer picture to guide ongoing care.3,5

That makes 14-3-3eta a valuable tool in both diagnosis and a “treat-to-target” approach, helping you and your doctor assess whether treatment is effective or needs to be adjusted.

In Juvenile Idiopathic Arthritis (JIA): A New Piece of the Puzzle

In children and teens with JIA, especially polyarticular JIA, diagnosis can be challenging—particularly when RF and anti-CCP are negative. That’s where 14-3-3eta can make a difference.

• It’s been found across all major JIA subtypes, including RF-positive, RF-negative, oligoarticular, systemic, and enthesitis-related JIA.6,7

• It’s especially helpful in RF-negative cases, where traditional tests often fall short.6,8

• Higher levels of 14-3-3eta are associated with more severe disease and a higher risk of joint damage.6,9,10

• In some children, early 14-3-3eta positivity preceded the development of other antibodies, suggesting it may help flag disease earlier.6,10

For young patients and their families, this means another tool to help get answers sooner and track disease progression more closely over time.

What This Means for Patients and Families

Understanding your biomarker profile—especially newer tools like 14-3-3eta—can help you take a more active role in your care. It opens the door to:

• More informed conversations with your rheumatologist

• Early insight into treatment response

• More personalized and proactive disease management

Looking Ahead

While no single test tells the whole story, 14-3-3eta adds valuable perspective, especially when used alongside existing markers. It helps doctors not only diagnose arthritis but also track it more precisely over time.

If you or your child is living with RA or JIA and want to know more about biomarkers that can help guide care, it’s worth asking your doctor about 14-3-3eta. 

References

1. Maksymowych WP, Naides SJ, Bykerk V, et al. Serum 14-3-3η is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis. J Rheumatol. 2014;41(11):2104-2113.

2. Naides SJ, Marotta A. 14-3-3η in “Seronegative” Rheumatoid Arthritis. J Rheumatol. 2015;42(10):1995.

3. Maksymowych WP, van der Heijde D, Allaart CF, et al. 14-3-3η is a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage. Arthritis ResTher. 2014;16(2).

4. Hirata S, Marotta A, Gui Y, Hanami K, Tanaka Y. Serum 14-3-3η level is associated with severity and clinical outcomes of rheumatoid arthritis, and its pretreatment level is predictive of DAS28 remission with tocilizumab. Arthritis Res Ther. 2015;17:280.

5. Carrier N, Marotta A, de Brum-Fernandes AJ, et al. Serum levels of 14-3-3η protein supplement C-reactive protein and rheumatoid arthritis-associated antibodies to predict clinical and radiographic outcomes in a prospective cohort of patients with recent-onset inflammatory polyarthritis. Arthritis Res Ther. 2016;18:3.

6. Dalrymple A, Tuttle P, Feller L, Zhukov O, Lagier R, Popov J, Naides S, Moore T. 14-3-3η Protein as a Potential Biomarker in Juvenile Idiopathic Arthritis. Pediatr Rep. 2021 Jan 25;13(1):65-71.

7. Reyhan I, Zhukov OS, Lagier RJ, et al. Prevalence and significance of serum 14-3-3η in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2021;19(1):14.

8. Rosenberg AM, Maksymowych W, Gui Y, Marotta A. Serum 14-3-3η Is Present in JIA and Is Not Associated with RF+ Polyarthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10).

9. Feller L, Dalrymple AM, Tuttle P IV, Syed RH, Pepmueller P, Moore T. Examination of the Clinical Significance of 14-3-3 Eta in Juvenile Idiopathic Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10).

10. Dalrymple AM, Tuttle P IV, Feller L, Zhukov OS, Lagier RJ, Bridgforth R, Williams GJ, Popov JM, Naides SJ, Moore T. 14-3-3η (eta) Protein in Juvenile Idiopathic Arthritis (JIA) Patients [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10).