Session Type: Abstract Submissions (ACR)
Background/Purpose: The 14-3-3 family of chaperonin proteins consists of 7 isomers. The tissue distribution of the 14-3-3η (eta) isoform is limited to synovial tissue and brain. 14-3-3η is released from synovial tissue into the synovial fluid and serum in patients with rheumatoid arthritis (RA) and, to a lesser extent, erosive psoriatic arthritis (ePsA). Extracellular 14-3-3η induces signaling pathways that lead to production of proinflammatory mediators including metal η loproteinases, RANKL, IL1, TNFα, and additional 14-3-3η, thereby exacerbating disease. Serum 14-3-3η measurement has been shown to aid diagnosis and prognosis of rheumatoid arthritis, and may have utility in assessing disease activity. The purpose of this study was to investigate the potential value of adding 14-3-3η to traditional biomarkers of rheumatoid factor (RF) and citrullinated cyclic peptide antibody (CCP).
Methods: Consecutive serum samples (n=1944) referred to an esoteric diagnostic laboratory for a “Rheumatoid Arthritis Diagnostic Panel” were tested for RF by nephelometry, CCP by immunoassay (INOVA QUANTA Lite™ CCP3.0 IgG ELISA), and 14-3-3η by a proprietary laboratory-developed test (ELISA).
Results: Of 1944 sera tested, 248 (12.8%; 95% CI 11.3%–14.3%,) were positive for 14-3-3η. 1483 of the 1944 samples (76.3%; 95% CI 74.3%–78.1%) were negative for both RF and CCP. Of these seronegative samples, 91 (6.1%; 95% CI 5.0%–7.5%) were positive for 14-3-3η. 14-3-3η was also in positive in 46 of 245 RF+/CCP- samples (18.8%; 95% CI 14.4%–24.1%); 107 of 161 RF+/CCP+ samples (66.5%, 95% CI 58.9%–73.3%); and only 4 of 55 RF-/CCP+ samples (7.3%, 95% CI 2.9%–17.3%).
Conclusion: Serum 14-3-3η was positive in 12.8% of individuals tested for RA biomarkers. The population likely includes individuals without RA, with seropositivity for RF and/or CCP but no joint disease, or with other rheumatic diseases; these factors may account for the lower rate of 14-3-3η positivity relative to that reported in clinically defined early RA. Further, 14-3-3η was positive in 18.8% of RF+/CCP- samples, suggesting that this marker may be useful in further demonstrating joint specificity of an isolated positive RF result. Adding 14-3-3η testing to RF and CCP increases detection of individuals warranting further evaluation for RA and possibly ePsA, and may assist primary care physicians in triaging referrals to rheumatologists. Subsequent studies with detailed clinical correlation are warranted.
C. M. Rowland,
J. M. Popov,
S. J. Naides,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-14-3-3%ce%b7-protein-supplements-traditional-rheumatoid-arthritis-biomarkers/