Background 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 (ePsA) patients. Serum measurement aids RA diagnosis (sensitivity 64% in early RA and 77% in established RA), prognosis, and may have utility in assessing disease activity.1,2 Differentiating RA or PsA from OA, or identifying inflammatory arthritis in the presence of co-existing OA can be difficult. Examination and traditional biomarkers may be insufficient, especially for physicians without specialized training and experience.
Objectives The purpose of this study was to estimate the specificity of 14-3-3η among a cohort of subjects with physician confirmed osteoarthritis.
Methods Subjects in the U.S.-based Arthritis Internet Registry (AIR) were surveyed by questionnaire. Physician and/or medical records were queried. Serum samples from subjects with physician confirmed diagnoses of osteoarthritis (n=166) were tested for CRP and rheumatoid factor (RF) by nephelometry, CCP by ELISA, and 14-3-3η by a proprietary laboratory-developed test (ELISA).
Results Of 166 physician diagnosed OA subjects tested, 11 (6.6%; 95% CI 3.7% to 11.5%) were positive for 14-3-3η. However, 1 of the 11 had CRP 0.3 mg/dL, (normal, <0.8 mg/dL), RF 123 IU/ml (normal <14 IU/mL), CCP >250 Units (normal, <20 Units), and 14-3-3η 1.9 ng/mL (normal, <0.2 ng/mL) and was subsequently reclassified as RA. Another subject had normal CRP, RF, and CCP, but 14-3-3η was 3.1 ng/mL and subsequently was diagnosed with PsA based on swelling in 2 fingers, joint pain and changes in fingernails, all in the absence of prior psoriasis. A third subject was physician-diagnosed as OA, but had previously been treated for RA with methotrexate and entanercept; CRP was 4.4 mg/dL, RF >1200 IU/mL, CCP >250 Units, and 14-3-3η >20 ng/mL. Excluding the 3 subjects with subsequent diagnoses of RA or PsA, 8 of 163 OA subjects were 14-3-3η positive, or 4.9% (95% CI 2.5% to 9.4%). The specificity in OA subjects for 14-3-3η as a marker of inflammatory arthritis was 95.1% (95% CI 90.6% to 97.5%).
Conclusions Serum 14-3-3η was positive in 6.6% of individuals with an initial physician diagnosis of OA, and 4.9% after exclusion of subjects with subsequent diagnoses of RA or PsA. We previously demonstrated a similarly low frequency of 14-3-3η in normal donors, several of whom had RF suggesting preclinical inflammatory disease.1 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.
Maksymowych, et al. J Rheum 2014;41:2104-13.
Maksymowych, et al. Clin Exp Rheum 2014;32(Suppl 85):S35-9.
Disclosure of Interest S. Naides Employee of: Quest Diagnostics, O. Zhukov Employee of: Quest Diagnostics, J. Rivera Employee of: Quest Diagnostics, R. Abolhosn Employee of: Quest Diagnostics, C. Rowland Employee of: Quest Diagnostics, J. Popov Employee of: Quest Diagnostics, K. Michaud: None declared