Background/Purpose

14-3-3 proteins are chaperonins found in all eukaryotic cells. There are multiple isoforms which are thought to be involved in intracellular signaling and transcription regulation. Among their targets are phosphatases, kinases and transmembrane receptors. There are seven known isoforms in mammals. Recent work has implicated the η (Eta) isoform as having diagnostic potential in inflammatory arthritis. In this study we investigated the utility of measuring 14-3-3η when evaluating of inflammatory arthritis.

Methods

Measurements of 14-3-3η were obtained during evaluation of joint pain in patients presenting between July 2013 and May of 2014. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab) were measured. Joint imaging was evaluated for erosive changes. A chart review was later conducted to evaluate the utility of standard measures versus 14-3-3η.

 Results

120 patients were evaluated. 21 had RA, 8 had juvenile idiopathic arthritis (JIA), and 6 had psoriatic arthritis (PsA). 30 patients had connective tissue disease (CTD). 10 had fibromyalgia (FMS), 3 had monoclonal gammopathies, 1 had enteropathic arthritis, and 1 had erosive osteoarthritis (OA). 8 had only OA, 2 had benign hypermobility syndrome, 1 had amyopathic dermatomyositis, 2 had celiac disease, and 2 had crystal induced arthropathies. 7 were antinuclear antibody (ANA) positive without synovitis or CTD. 3 patients had granulomatosis with polyangiitis, 2 had suspected PsA, 2 had chronic urticaria, and 11 had no associated condition.

Of the 21 RA patients, 18 were RF positive, 16 were anti-CCP Ab positive, and 16 were 14-3-3η positive. All 16 14-3-3η positive patients with RA were RF positive. 9 had joint erosions, of which 8 were RF, anti-CCP Ab and 14-3-3η positive. 14-3-3η was 76.2% sensitive for RA, and 89% specific. Its positive predictive value (PPV) was 61.5%, and negative predictive value (NPV) was 94.2%. 4 of the 8 JIA patients were 14.3.3η and RF positive. 4 were also anti-CCP Ab positive, of which 2 had measurable 14-3-3η. 3 JIA patients had joint erosions. When JIA and RA were considered together, the sensitivity and specificity of 14-3-3η was 68.9 and 89% respectively, while PPV and NPV were 66.7 and 90%. The correlation of 14-3-3η and RF titers in RA was 0.63 (p<0.01) and 0.65 (p<0.001) in the combined RA/JIA cohort.

All 6 patients with PsA were seronegative. 2 had joint erosions.

30 patients had CTD; 6 were RF positive, 2 were anti-CCP Ab positive, and 5 were 14-3-3η positive. 3 of the five 14-3-3η positive patients also produced RF, while 1 had anti-CCP Ab.

All FMS patients were seronegative. Of the 8 patients with purely OA, 1 had 14-3-3η. 1 patient with celiac disease had 14-3-3η. 1 patient with a positive ANA and joint pain had 14-3-3η. 1 patient with joint pain and no evidence of synovitis produced 14-3-3η.

Of the 17 patients with RF without RA, 10 were positive for 14-3-3η, while 6 produced anti-CCP Ab.

Conclusion

14-3-3η protein titers are associated with RA. Their general trend follows RF. Based upon the results from our study, 14-3-3η is both sensitive and specific for RA, with value in evaluating JIA as well. A larger sample size is necessary to evaluate utility with JIA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-utility-of-14-3-3%ce%b7-in-the-evaluation-of-inflammatory-arthritis/