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. Recent work has implicated the η (eta) isoform as having diagnostic potential in inflammatory arthritides. Its utility in JIA has not been established. Our preliminary prior investigation indicated positivity in some JIA patients. In this study, we investigated a much larger cohort of patients with JIA and disease and healthy controls.

Methods: Measurement of 14-3-3η protein was evaluated in 29 rheumatoid factor (RF) positive (pos) polyarticular (poly) JIA patients, 29 RF negative (neg) poly patients, 34 oligoarticular (oligo) patients, 12 systemic-onset (SO) patients, 19 adult rheumatoid arthritis (RA) patients, 60 patients with systemic lupus (SLE), and 20 healthy controls by the assay established at Quest Diagnostics. Comparisons were made to CBC, ESR, CRP, RF and anti-CCP isotypes, and ANA positivity.

Results: 14-3-3η at 0.2 ng/ml or higher was considered positive; values of 0.5 ng/mL or greater have been considered prognostic of poor outcome in adults. Ten of 29 (34%) RF pos polys were positive for the 14-3-3η protein; 8 (28%) had values > 0.5 ng/mL. Nine of 29 (31%) RF neg polys were positive; 8/29 (28%) had values >0.5 ng/mL. Only 6/34 (18%) oligos were positive; 5/34 (15%) >0.5 ng/mL. Only 2/12 (16%) SO were positive; 1/12 (8%) >0.5 ng/mL. In the disease controls, 14/60 (23%) SLE were positive, but only 7/60 (12%) >0.5 ng/mL. 7/19 RA patients were positive, 4/19 (21%) >0.5 ng/mL. In the healthy controls, only 3/20 (15%) were positive, 1/20 (5%) > 0.5 ng/mL. The RF pos and RF neg polys positivity, especially at values >0.5 ng/mL compared favorably with the adult RA patient and were significant compared to disease and healthy controls. A weak correlation was noted between 14-3-3η positivity and CRP. Five of the 8 RF neg polys at original diagnosis that were 14-3-3η positive at >0.5 ng/mL have subsequently developed a positive RF and an anti-CCP antibody isotype. Also, the one SO positive for 14-3-3η >0.5 ng/mL also developed a positive RF.

Conclusion:  Significant levels of 14-3-3η protein can be found in about 30% of RF pos and RF neg poly JIA patients. It may represent a new biomarker for RF neg poly JIA patients and a marker indicating the possibility of these patients becoming RF/anti-CCP antibody positive in the future. Further longitudinal studies are required to confirm these findings.