RT Journal Article
SR Electronic
T1 14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1587
OP 1594
DO 10.3899/jrheum.141385
VO 42
IS 9
A1 Walter P. Maksymowych
A1 Gilles Boire
A1 Dirkjan van Schaardenburg
A1 Stephanie Wichuk
A1 Samina Turk
A1 Maarten Boers
A1 Katherine A. Siminovitch
A1 Vivian Bykerk
A1 Ed Keystone
A1 Paul Peter Tak
A1 Arno W. van Kuijk
A1 Robert Landewé
A1 Desiree van der Heijde
A1 Mairead Murphy
A1 Anthony Marotta
YR 2015
UL http://www.jrheum.org/content/42/9/1587.abstract
AB Objective. To describe the expression and diagnostic use of 14-3-3η autoantibodies in early rheumatoid arthritis (RA).Methods. 14-3-3η 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). 14-3-3η 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 14-3-3η 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 14-3-3η autoantibodies to 14-3-3η protein positivity enhanced the identification of patients with early RA from 59% to 90%; addition of 14-3-3η 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 14-3-3η autoantibodies.Conclusion. 14-3-3η autoantibodies, alone and in combination with the 14-3-3η protein, RF, and/or ACPA identified most patients with early RA.