14-3-3η Biomarker

Serial decrease/clearance predicts better radiographic outcomes in Rheumatoid Arthritis (RA)


Rheumatoid arthritis is a chronic, common, inflammatory autoimmune disease affecting about 1% of the population worldwide.1,2
Prognosis is dependent on early, accurate diagnosis and establishing an effective treatment plan.3
Diagnosis and classification of RA has relied heavily on the presence of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) IgM.4
However, about 28% of patients are seronegative for both anti-CCP and RF IgM in early RA and 12% seronegative in established RA.5 New markers
are needed to better identify early RA patients, stratify patients for risk of joint destruction, and to monitor disease activity and effectiveness of treatment.

14-3-3η — New “Complimentary” Biomarker

14-3-3η is an isoform of a family of proteins involved in the regulation of biologic activity of intracellular proteins.6 The 14-3-3η protein is released into the blood during synovial inflammation and is associated with the upregulation of factors leading to joint damage.3 Recent studies have found that 14-3-3η can be useful in helping make a diagnosis in both early and established RA3, in identifying RA patients seronegative for anti-CCP and RF5, and for monitoring clinical response to treatment7 as well as the risk of radiographic progression.8 14-3-3η has also been found to be predictive of erosive disease in Psoriatic Arthritis patients (PSA).9


• More accurate diagnosis of early RA3
• Increases sensitivity for identifying early RA to ≈ 80% when used in conjunction with anti-CCP and RF IgM3
• Helps diagnose RA in seronegative (anti-CCP- and RF-) patients3,8
• Monitoring clinical improvement in RA: 14-3-3η decrease with a persistent negative level is associated with less radiographic progression7,8
• Expression of 14-3-3η is independent of ESR and CRP, making it a useful monitor of clinical activity8
• Predictive of erosive disease in Psoriatic Arthritis (PSA)9


Test Code [1433]
Test Name RAdx3TM Panel (includes 14-3-3η, anti-CCP IgG/IgA, RF IgM)
Components 14-3-3η protein Ref Range: <0.2 ng/mL
  Anti-CCP, IgG/IgA Ref Range: <20 Units
  Rheumatoid Factor, IgM Ref Range: <=6IU
Specimen Requirements/Stability 3mL (1 mL min) Serum or Plasma; Ambient, Refridgerated or Frozen
Stable 4 days ambient, 14 days refridgerated, 3 months frozen
Methodology EIA, EIA, TURB
Turnaround Time 4-5 days


• [143] 14-3-3η Protein
• [1836] Rheumatoid Arthrtitis Antibody Panel, Comprehensive: anti-CCP IgG/IgA; RF IgM


1. Gibofsky, Allan. “Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis.” The American Journal of Managed Care 18.13 Suppl (2012): S295-302.
2. Chung, Ill-Min, et al. “Rheumatoid Arthritis: The Stride from Research to Clinical Practice.” International Journal of Molecular Sciences 17.6 (2016): 900.
3. Maksymowych, Walter P., et al. “Serum 14-3-3 etaη is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis.” The Journal of Rheumatology 41.11 (2014): 2104-2113.
4. Aletaha, Daniel, et al. “2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.” Arthritis & Rheumatism 62.9 (2010): 2569-2581.
5. Naides, Stanley J., and Anthony Marotta. “14-3-3 etaη in “Seronegative” Rheumatoid Arthritis.” The Journal of Rheumatology 42.10 (2015): 1995-1995.
6. Paul, G., and H. van Heusden. “14‐3‐3 eta Proteins: Regulators of numerous eukaryotic proteins.” IUBMB life 57.9 (2005): 623-629.
7. Hirata, Shintaro, et al. “Serum 14-3-3 etaη level is associated with severity and clinical outcomes of rheumatoid arthritis, and its pretreatment level is predictive of DAS28 remission with tocilizumab.” rthritis Research & Therapy 17.1 (2015): 1.
8. Carrier, Nathalie, et al. “Serum levels of 14-3-3 etaη 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 Research & Therapy 18.1 (2016): 1.
9. Marotta, A., et al. “SAT0309 Serum 14-3-3 eta: An independent biomarker associated with joint damage in psoriatic arthritis.” Annals of the Rheumatic Diseases 71.Suppl 3 (2013): 576-576.