Background/Purpose: Tissue distribution of the chaperonin 14-3-3η (eta) is limited to synovial tissue and brain. Synovium releases proinflammatory 14-3-3η into synovial fluid and serum in rheumatoid arthritis (RA) patients and, to a lesser extent, erosive psoriatic arthritis (PsA) patients. Serum measurement aids RA diagnosis (sensitivity 64% in early RA and 77% in established RA) and prognosis, and may have utility in assessing disease activity.^1,2  Differentiating RA or PsA from osteoarthritis (OA), or identifying inflammatory arthritis in the presence of co-existing OA can be difficult. The purpose of this study was to estimate the specificity of 14-3-3η among a cohort of subjects with physician-confirmed OA.

Methods: Participants in the U.S.-based Arthritis Internet Registry (AIR) were surveyed by questionnaire. Physician and/or medical records were queried. Serum samples from patients with physician-confirmed diagnoses of OA (n=169) were tested for C-reactive protein (CRP) and rheumatoid factor (RF) by nephelometry, cyclic citrullinated peptide antibody (CCP) by ELISA, and 14-3-3η by a proprietary laboratory-developed ELISA test.

Results:  Of 169 physician-diagnosed OA patients tested, 11 (6.5%; 95% CI 3.3% to 11.3%) were positive for 14-3-3η. However, for 1 of the 11, CRP was 0.3 mg/dL, (normal, <0.8 mg/dL), RF was 123 IU/ml (normal <14 IU/mL), CCP was >250 Units (normal, <20 Units), and 14-3-3η was 1.9 ng/mL (normal, <0.2 ng/mL); the subject was subsequently reclassified as RA. Another subject’s CRP, RF, and CCP were nomral, but 14-3-3η was 3.1 ng/mL; subsequently, the subject was diagnosed with PsA based on new onset dactylitis in 2 fingers, joint pain, and changes in fingernails, all in the absence of prior psoriasis. A third subject had previously been treated for RA with methotrexate and entanercept; CRP was 4.4 mg/dL, RF was >1,200 IU/mL, CCP was >250 Units, and 14-3-3η was >20 ng/mL. Excluding the 3 subjects with subsequent diagnoses of RA or PsA, 8 of 166 OA subjects were 14-3-3η positive, or 4.8% (95% CI 2.1% to 9.3%). The specificity in OA subjects for 14-3-3η as a marker of inflammatory arthritis was 95.2% (95% CI 90.7% to 97.9%).

Conclusion:   In the present study, the low frequency of 14-3-3η in a cohort of individuals with OA supports the high specificity of 14-3-3η observed for RA. Further, 14-3-3η may be used to help identify RA or PsA patients amongst those being followed for OA. 14-3-3η may be particularly useful in the primary care setting to screen OA patients for misclassification of RA or PsA as OA, or for concurrent inflammatory arthritis in the setting of OA. 

References:  1. Maksymowych, et al. J Rheum. 2014;41:2104-13; 2. Maksymowych, et al. Clin Exp Rheum. 2014;32(Suppl 85):S35-9.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-14-3-3eta-protein-elevation-in-osteoarthritis-suggests-misclassification-or-concurrent-inflammatory-arthritis/