Background Serum 14-3-3 eta has been described to have diagnostic utility and in established RA an association has been established between the levels of this marker and the degree of joint damage. The η isoform of 14-3-3 is expressed extracellularly in much higher concentration than the Υ isoform or MMP 1 and 3 levels in the synovial fluid and serum of patients with rheumatoid arthritis compared to the normal population. Rheumatoid factor (RF) is known to be sensitive and anti CCP highly specific for RA, but a high number of patients remain seronegative. There is a need for a biomarker to prevent underdiagnosis in this subset.
Objectives The purpose of the study was to investigate if serum 14-3-3 η enhanced the detection of RA over RF or anti CCP in RA patients. We also studied the utility of 14-3-3 eta as a diagnostic test by comparing presence of this protein in RA v/s non-RA patients.
Methods A retrospective chart review study was conducted in RA patients at an outpatient rheumatology clinic in an inner city population at a community teaching hospital serving a large immigrant population. 91 RA patients were identified who satisfied the 2010 ACR diagnostic criteria and 37 non RA patients seen in the clinic for other rheumatologic conditions were chosen as the control group. Serum 14-3-3η protein was measured by ELISA. The positive threshold range using Quest Diagnostic for RF was 15 International Unit/ml, Anti CCP was 20 Units and for 14-3-3 eta was 0.2 ng/mL. The chi-square goodness-of-fit test was used to analyze the frequency of eta positivity in the RA population while kappa was calculated to compare the RA and non RA patients.
Results Of the 91 RA patients, 75.8% were females and mean age was 58 (range 28- 90) years. The population was predominantly Hispanic (75%). In the non-RA group, 9% had psoriatic arthritis and 14% lupus, 73% were females,76% Hispanic and the mean age was 54 (range 19-93) years. In the RA population, none of group without RF or anti-CCP was positive for eta. For those with either RF or anti-CCP, the prevalence of eta positivity was 11.1% (95%CI 2.8-35.2%). For those with both RF and anti-CCP, the prevalence of eta positivity was 81.0% (95% CI 68.9-89.2%). All comparisons between groups were significant at p<0.001. When comparing RA vs. non-RA, the kappa calculated was 0.016 (95% confidence interval: -0.047 to 0.078), the strength of agreement is considered to be poor. The sensitivity, specificity, positive predictive value, and negative predictive value for all RA patients was 0.54, 0.73, 0.83, and 0.39, respectively. The Sn, Sp, PPV, and NPV just for RF+CCP+ (i.e. both positive) was 0.82, 0.81, 0.76, and 0.85, respectively.
Conclusions Measurement of 14-3-3η complements RF and anti-CCP antibody tests in RA and may improve diagnostic sensitivity. Used in combination with other serological markers, 14-3-3 eta can increase identification of patients with RA.
Disclosure of Interest None declared