Test Id : 1433E
14-3-3 eta, Serum
Useful For
Suggests clinical disorders or settings where the test may be helpful
A potentially improved approach for the early identification of patients at-risk for or with early and established rheumatoid arthritis (RA) in combination with specific autoantibody tests
This test is intended to be used as an aid in the early diagnosis of RA and management of the disease.
Method Name
A short description of the method used to perform the test
Enzyme-Linked Immunosorbent Assay (ELISA)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
14-3-3 eta
Specimen Type
Describes the specimen type validated for testing
Serum SST
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Supplies: Sarstedt Aliquot Tube 5 mL (T914)
Collection Container/Tube: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 0.5 mL Serum
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
Serum: 0.4 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | Reject |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum SST | Refrigerated (preferred) | 14 days | |
| Ambient | 48 hours | ||
| Frozen | 100 days |
Useful For
Suggests clinical disorders or settings where the test may be helpful
A potentially improved approach for the early identification of patients at-risk for or with early and established rheumatoid arthritis (RA) in combination with specific autoantibody tests
This test is intended to be used as an aid in the early diagnosis of RA and management of the disease.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Serum 14-3-3 eta protein belongs to the 14-3-3 family of intracellular chaperone proteins (beta, gamma, epsilon, eta, sigma, theta, zeta). It is a joint-derived proinflammatory mediator that up-regulates cytokines and enzymes that perpetuate local and systemic inflammation and may contribute to joint damage.
Serum 14-3-3 eta is detectable at significantly higher levels in the serum from patients with rheumatoid arthritis (RA) when compared to healthy subjects and individuals with RA mimickers (other autoimmune conditions and viral/bacterial infections). It has also been reported as an important biomarker in diagnosing cases that are seronegative for traditional markers like rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA).
In addition to the contribution of 14-3-3 eta in the diagnosis of RA, previous studies have reported its clinical potential of 14-3-3 eta as a predictor of poor clinical and radiographic outcomes, both at baseline and after initiation of treatment, even in Simplified Disease Activity Index (SDAI) remitters. These studies suggest that 14-3-3 eta, c-reactive protein, age, and ACPA represent independent predictors of subsequent joint damage.
Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< 0.19 ng/mL
Interpretation
Provides information to assist in interpretation of the test results
Serum 14-3-3 eta was tested in a clinically characterized rheumatoid arthritis (RA) and early RA patient Mayo Clinic patient cohort, where 275 of 446 patients (82.6%) were seropositive (defined as having 3rd generation anti-CCP IgG antibody [CCP3] >20 U and/or rheumatoid factor [RF] >14 IU/mL). A 14-3-3 eta cutoff of > or =0.19 ng/mL for both early and established RA patients was used to calculate the sensitivity and specificity of 14-3-3 eta for RA (n=113) and early RA (n=95).
Serum 14-3-3 eta slightly increased sensitivity for RA (87.0%) and early RA (75.8%) when used in concert with anti-CCP3 IgG and RF, versus the use of a combination of anti-CCP3 IgG and RF alone (RA sensitivity 82.6%, and early RA sensitivity 74.7%).
The addition of 14-3-3 eta offers an increase in specificity for RA (99.1%), and early RA (99.1%), relative to observed positivity with RF and anti-CCP3 IgG antibodies without the use of 14-3-3 eta (RA specificity 94.7%, and early RA specificity 94.7%).
| Serum 14-3-3 eta concentration (ng/mL) | Qualitative Interpretation |
| <0.19 | Negative |
| > or =0.19-0.39 | Mild positive |
| > or =0.40-0.79 | Moderate positive |
| > or =0.80 | Strong positive |
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A test result that is inconsistent with the clinical picture and patient history should be interpreted with caution.
In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies or heterophile antibodies) that may cause interference in some immunoassays. Caution should be used in interpretation of results, and the laboratory should be alerted if the result does not correlate with the clinical presentation.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Kilani RT, Maksymowych WP, Aitken A, et al. Detection of high levels of 2 specific isoforms of 14-3-3 proteins in synovial fluid from patients with joint inflammation. J Rheumatol. 2007;34(8):1650-1657
2. Maksymowych WP, Naides SJ, Bykerk V, et al. Serum 14-3-3 eta is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis. J Rheumatol. 2014;41(11):2104-2113
3. Guan SZ, Yang YQ, Bai X, et al. Serum 14-3-3 eta Could Improve the Diagnostic Rate of Rheumatoid Arthritis and Correlates to Disease Activity. Ann Clin Lab Sci. 2019;49(1):57-62
4. Subedi R, Misbah A, Najada AA, Ocon AJ. Evaluation of 14-3-3eta protein as a diagnostic biomarker in the initial assessment of inflammatory arthritis. J Rheum Dis. 2025;32(2):130-135
5. Shovman O, Gilburd B, Watad A, et al. The diagnostic value of 14-3-3 eta protein levels in patients with rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2018;32(4):610-617
6. Maksymowych WP, Boire G, van Schaardenburg D, et al. 14-3-3? Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis. J Rheumatol. 2015;42(9):1587-1594
7. Carrier N, Marotta A, de Brum-Fernandes AJ, et al. Serum levels of 14-3-3 eta 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;18:37
8. Hammam N, Salah S, Kholef EF, Moussa EM, Marotta A. 14-3-3 eta Protein in serum and synovial fluid correlates with radiographic damage and progression in a longitudinal evaluation of patients with established rheumatoid arthritis. Mod Rheumatol. 2020;30(4):664-670
9. Nelson HA, Martins TB, Saadalla A, Nandakumar V. Evaluation of the clinical performance of anti-mutated citrullinated vimentin antibody and 14-3-3 eta testing in rheumatoid arthritis. Clin Chem Lab Med. 2024;63:790-796
Method Description
Describes how the test is performed and provides a method-specific reference
The JOINTstat 14-3-3 eta enzyme-linked immunosorbent assay is an immunoassay that uses a microtiter plate coated with a murine monoclonal antibody specific for human 14-3-3 eta, a horseradish peroxidase (HRP)-conjugated monoclonal antibody, and a chromogenic substrate. When standards, diluted controls, and diluted patient specimens are added to the coated wells, any 14-3-3 eta present binds to the immobilized antibody. After an incubation period, the wells are washed to remove material that did not bind. An HRP-conjugated anti-14-3-3 eta antibody is then added. This conjugate binds to the captured 14-3-3 eta, forming a detectable complex. Following incubation, another wash cycle removes unbound conjugate. A chromogenic substrate is introduced, and the HRP enzyme converts the substrate into a colored product that initially appears blue. When the reaction is stopped, the color changes to yellow. The absorbance at 450 nm is measured and is proportional to the concentration of 14-3-3 eta present in the standards, controls, and patient samples.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Wednesday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
83520
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| 1433E | 14-3-3 eta, S | 75880-5 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 624066 | 14-3-3 eta, S | 75880-5 |