14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis

Objective. To describe the expression and diagnostic use of 14-3-3 eta autoantibodies in early rheumatoid arthritis (RA). Methods. 14-3-3 eta autoantibody levels were measured using an electrochemiluminescent multiplexed assay in 500 subjects (114 disease-modifying antirheumatic drug-naive patients with early RA, 135 with established RA, 55 healthy, 70 autoimmune, and 126 other non-RA arthropathy controls). 14-3-3 eta protein levels were determined in an earlier analysis. Two-tailed Student t tests and Mann-Whitney U tests compared differences among groups. Receiver-operator characteristic (ROC) curves were generated and diagnostic performance was estimated by area under the curve (AUC), as well as specificity, sensitivity, and likelihood ratios (LR) for optimal cutoffs. Results. Median serum 14-3-3 eta autoantibody concentrations were significantly higher (p < 0.0001) in patients with early RA (525 U/ml) when compared with healthy controls (235 U/ml), disease controls (274 U/ml), autoimmune disease controls (274 U/ml), patients with osteoarthritis (259 U/ml), and all controls (265 U/ml). ROC curve analysis comparing early RA with healthy controls demonstrated a significant (p < 0.0001) AUC of 0.90 (95% CI 0.85-0.95). At an optimal cutoff of >= 380 U/ml, the ROC curve yielded a sensitivity of 73%, a specificity of 91%, and a positive LR of 8.0. Adding 14-3-3 eta autoantibodies to 14-3-3 eta protein positivity enhanced the identification of patients with early RA from 59% to 90%; addition of 14-3-3 eta autoantibodies to anticitrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) increased identification from 72% to 92%. Seventy-two percent of RF-and ACPA-seronegative patients were positive for 14-3-3 eta autoantibodies. Conclusion. 14-3-3 eta autoantibodies, alone and in combination with the 14-3-3 eta protein, RF, and/or ACPA identified most patients with early RA.