Our Science

Our 14-3-3eta biomarker portfolio features the joint-derived 14-3-3eta protein and its autoantibodies, providing insights into the disease mechanisms of inflammatory autoimmune conditions, including rheumatoid arthritis and axial spondyloarthritis.

14-3-3et-Mechanism--3

14-3-3eta Biomarker Portfolio: Precision Diagnostics for Rheumatoid Arthritis and Axial Spondyloarthritis

The 14-3-3eta protein is a joint-derived intracellular protein involved in essential cell functions. During joint inflammation, it is externalized and acts as a proinflammatory ligand, driving further joint erosion and damage.

Its utility as a biomarker was established when elevated levels in serum and synovial fluid were shown to be highly specific to rheumatoid arthritis (RA), distinguishing it from other inflammatory conditions and arthritides. The presence of 14-3-3eta was prominently linked to active joint inflammation and damage risk. As 14-3-3eta levels fluctuate, it helps monitor disease activity and response to treatment, providing insights into ongoing joint damage risk in RA.

Autoantibodies to 14-3-3eta epitopes (anti-14-3-3eta) have also been identified as a novel biomarker for diagnosing axial spondyloarthritis (axSpA), which when used in a diagnostic test could reduce the typically extensive delay in diagnosis and enable earlier intervention.

jointstat+spinestat

Learn more about how our products can transform patient outcomes. Our testing solutions feature the 14-3-3eta test for diagnosing and monitoring rheumatoid arthritis (JOINTstat), as well as our first-in-class diagnostic test for axial spondyloarthritis (SPINEstat).

Publications

Rheumatoid Arthritis

Over 10 years of peer reviewed research

14-3-3η Mechanism of Action

14-3-3η is a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage

Maksymowych W et al.

Arthritis Research & Therapy, 2014

14-3-3η Promotes Invadosome Formation via the FOXO3–Snail Axis in Rheumatoid Arthritis Fibroblast-like Synoviocytes

Kadiri M et al.

International Journal of Molecular Sciences, 2021

Tumour necrosis factor alpha promotes secretion of 14-3-3η by inducing necroptosis in macrophages

Trimova G et al.

Arthritis Research & Therapy, 2020

Risk of RA

A prospective cohort study of 14-3-3η in ACPA and/or RF-positive patients with arthralgia

van Beers-Tas M et al.

Arthritis Research & Therapy, 2016

Serum 14-3-3eta Are Elevated in Indigenous North Americans with Rheumatoid Arthritis and May Predict Imminent Synovitis in Their at-Risk First Degree Relatives

Hitchon C et al.

Arthritis & Rheumatology, 2015

Diagnosis

Serum 14-3-3η is a Novel Marker that Complements Current Serological Measurements to Enhance Detection of Patients with Rheumatoid Arthritis

Maksymowych W et al.

The Journal of Rheumatology, 2014

14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis

Maksymowych W et al.

The Journal of Rheumatology, 2015

The Diagnostic Value of 14-3-3η Protein Levels in Patients with Rheumatoid Arthritis

Shovman O et al.

Best Practice & Research Clinical Rheumatology, 2018

Serum 14-3-3η Protein is Associated with Clinical and Serologic Features of Sjögren’s Syndrome in Patients with Systemic Lupus Erythematosus: A Cross-Sectional Analysis

Hammam N et al.

Clinical Rheumatology, 2020

14-3-3 Eta protein as a novel biomarker in early detection of uveitis in Egyptian juvenile idiopathic arthritis and rheumatoid arthritis patients: Diagnostic and prognostic value

Saif D et al.

Rheumatology and Immunology Research, 2025

Prognosis

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

Carrier N et al.

Arthritis Research & Therapy, 2016

Impending Radiographic Erosive Progression Over the Following Year in a Cohort of Consecutive Patients with Inflammatory Polyarthritis: Prediction by Serum Biomarkers

Carrier N et al.

RMD Open, 2020

Serum 14-3-3η as predictor of clinical remission and progression of structural damage in early rheumatoid arthritis following a treat-to-target strategy in a randomized controlled trial

Raft M et al.

Scandinavian Journal of Rheumatology, 2023

Monitoring

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

Hirata S et al.

Arthritis Research & Therapy, 2015

Decrease in 14-3-3η protein levels is correlated with improvement in disease activity in patients with rheumatoid arthritis treated with Tofacitinib

Shovman O et al.

Pharmacological Research, 2019

Correlation of Plasma 14-3-3η Levels with Disease Activity Measures in Methotrexate-Naïve RA Patients Treated with Upadacitinib Monotherapy in the Select-Early Phase 3 Study

Sornasse T et al.

Annals of the Rheumatic Diseases, 2020

Systematic Review & Meta-Analysis

Diagnostic accuracy of 14-3-3η protein in rheumatoid arthritis: A meta-analysis

Wang D et al.

International Journal of Rheumatic Diseases, 2020

The role of 14-3-3 eta as a biomarker in rheumatoid arthritis

Abdelhafiz D et al.

Rheumatology and Immunology Research, 2021

14-3-3eta: a novel biomarker platform for rheumatoid arthritis

Maksymowych W et al.

Clinical and Experimental Rheumatology, 2014

Axial Spondyloarthritis

Newest addition to our portfolio

Diagnosis

Autoantibodies to 14-3-3η Are Novel Biomarkers Associated with Inflammation and Radiographic Progression in Ankylosing Spondylitis

Maksymowych W et al.

ACR/ARHP Annual Meeting, 2014

Autoantibodies to 14-3-3η to Axial Spondyloarthritis

Marotta A et al.

Annals of the Rheumatic Diseases, 2024

14-3-3 eta Auto-Antibody as a Diagnostic Marker in Axial Spondyloarthritis: A Longitudinal Study

Marotta A et al.

Arthritis & Rheumatology, 2024

Validation of anti-14-3-3η (eta) multiplex laboratory developed test (LDT) for the diagnosis of axial spondyloarthritis (axSpA)

Marotta A et al.

Annals of the Rheumatic Diseases, 2025

The 14-3-3η autoantibody assay combines with CRP and HLA-B27 to maximize the identification of patients with axial spondyloarthritis including in HLA-B27 negative patients; A validation study

Marotta A et al.

Annals of the Rheumatic Diseases, 2025

Autoantibodies to 14-3-3 eta: A Novel Diagnostic Biomarker for Axial Spondyloarthritis

Sengupta R et al.

Arthritis & Rheumatology, 2025

Evaluating the Diagnostic Utility of 14-3-3 eta Autoantibodies in Axial Spondyloarthritis: A Multiplex Assay Approach

Marotta A et al.

Arthritis & Rheumatology, 2025

The 14-3-3 eta AAb biomarker improves discriminative performance of CRP and HLA-B27 to differentiate people with radiographic axSpA from those with mechanical back pain

Maksymowych W et al.

Arthritis & Rheumatology, 2025

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