RAdx5-logo

Including 14-3-3η, CEP-1, Sa

Enhances the diagnosis of Rheumatoid Arthritis (RA) in early or seronegative disease and helps predict disease severity and radiographic progression

The RAdx5™ is a novel comprehensive diagnostic and prognostic panel for rheumatoid arthritis (RA) available exclusively at RDL. It combines 3 novel markers (14-3-3η, anti-CEP-1 and anti-Sa) with 2 traditional markers (anti-CCP and RF-IgM) to not only enhance the diagnosis of RA in early or seronegative disease, but also to help predict disease severity. If 14-3-3η and/or anti-Sa positivity is present, the disappearance or decrease of these markers with treatment is associated with less radiographic progression.1-3 In pre-clinical RA, positivity of anti-CEP–1 along with anti-CCP antibodies significantly raises the risk of imminently developing clinical RA (odds ratio of 125)4.

CLINICAL UTILITY

  • May help identify RA in CCP- and RF-negative patients:
    In 50 seronegative RA patients (negative for IgM-RF, anti-CCP, 14-3-3η), checking for anti-Sa and anti-CEP-1 antibodies identified an additional 10% of patients5
  • May help diagnose early RA: anti-CEP-1 antibodies appear an average of 5.5 years before onset of RA symptoms4
  • Anti-CEP-1 IgG is highly specific for RA: Specificity 98%; Sensitivity 37-62%6
  • Anti-Sa is highly specific for RA: Specificity >95%7,8 In established RA, the Sensitivity is approx. 40%8
  • Anti-Sa positivity is associated with a poor prognosis, predicting a more aggressive and rapid disease course.
  • When anti-CCP antibodies are present in conjunction with anti-Sa, the PPV for RA increases to 98.1%9
  • Monitoring clinical improvement in RA: 14-3-3ηηand/or anti-Sa decrease to a persistent negative level is associated with less radiographic progression1,2
  • Expression of 14-3-3ηηis independent of ESR or CRP, making it a useful monitor of clinical activity2

ORDERING INFORMATION

[1224] RAdx5™ Available Exclusively at RDL!
Reference Range:

Result Notes:
Test Method Reference Range
14-3-3η protein EIA <0.2 ng/mL
Anti-CEP 1 IgG (EIA) EIA <20 Units
Anti-Sa IgG (EIA) EIA <20 Units
Rheumatoid Factor IgM TURB <= 6 IU
Anti-CCP Ab (EIA) EIA <20 Units
 
RAdx5, EIA Interpretation:
<20 Units Negative
20-39 Units Weak Positive
40-80 Units Moderate Positive
>80 Units Strong Positive
 
This panel was developed and its performance characteristics validated by RDL. There is no FDA approved assay for the above tests. As a lab developed test (LDT), approval or clearance by the FDA is not required. This test may be used for clinical purposes and should not be regarded as investigational or for research.
 
Specimen Requirements/Stability 3mL (1 mL min) Serum or Plasma; Ambient, Refrigerated or Frozen
Methodology EIA, TURB
Setup/TAT 3-4 days
CPT Code 83520 x3; 86200, 86431

RELATED TESTS

• [143] 14-3-3η Protein
• [1836] Rheumatoid Arthrtitis Antibody Panel, Comprehensive: anti-CCP IgG/IgA; RF IgM
• [177] Anti-Sa IgG (EIA) Available Exclusively at RDL!
• [178] Anti-CEP-1 IgG (EIA) Available Exclusively at RDL!

REFERENCES

1. 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.
2. 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.
3. Kastbom, A., et al. (2014). Changes in the anticitrullinated peptide antibody response in relation to therapeutic outcome in early rheumatoid arthritis: results from the SWEFOT trial. Annals of the rheumatic diseases, annrheumdis-2014.
4. Brink, M., et al. (2013). Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of Rheumatoid Arthritis. Arthritis & Rheumatism, 65(4), 899-910.
5. Karayev D, Shen G, Lam Y, Rimmer A, Lal N, Karayev E, Azarraga K, Blum RA, Metzger AL, Morris RI, Horizon AA. Sensitivity and Specificity of 14-3-3η, Anti-CEP-1 and Anti-Sa Antibodies in a Cohort of Seronegative and Suspected Rheumatoid Arthritis(RA) Patients from a Community Rheumatology Practice [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10).
6. Lundberg, K., et al. (2008). Antibodies to citrullinated enolase peptide 1 are specific for rheumatoid arthritis and cross‐react with bacterial enolase. Arthritis & Rheumatism, 58(10), 3009-3019.
7. El-Gabalawy, H. S., & Wilkins, J. A. (2004). Anti-Sa antibodies: prognostic and pathogenetic significance to rheumatoid arthritis. Arthritis Res Ther, 6(2), 1.
8. Ménard, H. A., Lapointe, E., Rochdi, M. D., & Zhou, Z. J. (2000). Insights into rheumatoid arthritis derived from the Sa immune system. Arthritis Research & Therapy, 2(6), 1.
9. Rodríguez Mahou, M., et al. (2006). Association of anti–cyclic citrullinated peptide and anti Sa/citrullinated vimentin autoantibodies in rheumatoid arthritis. Arthritis Care & Research, 55(4), 657-661.