Walter P Maksymowych1, Gilles Boire2, Dirkjan van Schaardenburg2, Stephanie Wichuk2, Samina Turk2, Maarten Boers2, Katherine A Siminovitch2, Vivian Bykerk2, Ed Keystone2, Paul Peter Tak2, Arno W van Kuijk2, Robert Landewé2, Desiree van der Heijde2, Mairead Murphy2, Anthony Marotta2. 1. From the Department of Medicine, University of Alberta, Edmonton, Alberta; Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Quebec; Mount Sinai Hospital, University of Toronto, Toronto; Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada; Jan van Breemen Research Institute/Reade; VU University Medical Center; Academic Medical Center, Amsterdam; Division of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Hospital for Special Surgery, New York, New York, USA; University of Cambridge, Cambridge; GlaxoSmithKline Inc., Brentford, UK.W.P. Maksymowych, MD, Professor of Medicine, Department of Medicine, University of Alberta; G. Boire, MD, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke; D. van Schaardenburg, MD, Jan van Breemen Research Institute/Reade; S. Wichuk, MD, Department of Medicine, University of Alberta; S. Turk, MD, Jan van Breemen Research Institute/Reade; M. Boers, MD, Professor of Clinical Epidemiology, VU University Medical Center; K.A. Siminovitch, MD, Professor of Medicine, Mount Sinai Hospital, University of Toronto; V. Bykerk, MD, Hospital for Special Surgery; E. Keystone, MD, Professor of Medicine, Mount Sinai Hospital, University of Toronto; P.P. Tak, MD, Academic Medical Center, and University of Cambridge, and GlaxoSmithKline Inc.; A.W. van Kuijk, MD; Robert Landewé, MD, Academic Medical Center; D. van der Heijde, MD, Division of Rheumatology, Leiden University Medical Center; M. Murphy, PhD; A. Marotta, PhD, Augurex Life Sciences Corp. walter.maksymowych@ualberta.ca. 2. From the Department of Medicine, University of Alberta, Edmonton, Alberta; Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Quebec; Mount Sinai Hospital, University of Toronto, Toronto; Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada; Jan van Breemen Research Institute/Reade; VU University Medical Center; Academic Medical Center, Amsterdam; Division of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Hospital for Special Surgery, New York, New York, USA; University of Cambridge, Cambridge; GlaxoSmithKline Inc., Brentford, UK.W.P. Maksymowych, MD, Professor of Medicine, Department of Medicine, University of Alberta; G. Boire, MD, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke; D. van Schaardenburg, MD, Jan van Breemen Research Institute/Reade; S. Wichuk, MD, Department of Medicine, University of Alberta; S. Turk, MD, Jan van Breemen Research Institute/Reade; M. Boers, MD, Professor of Clinical Epidemiology, VU University Medical Center; K.A. Siminovitch, MD, Professor of Medicine, Mount Sinai Hospital, University of Toronto; V. Bykerk, MD, Hospital for Special Surgery; E. Keystone, MD, Professor of Medicine, Mount Sinai Hospital, University of Toronto; P.P. Tak, MD, Academic Medical Center, and University of Cambridge, and GlaxoSmithKline Inc.; A.W. van Kuijk, MD; Robert Landewé, MD, Academic Medical Center; D. van der Heijde, MD, Division of Rheumatology, Leiden University Medical Center; M. Murphy, PhD; A. Marotta, PhD, Augurex Life Sciences Corp.
Abstract
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.
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.
Authors: Shaimaa A Fattah; Maha A Abdel Fattah; Noha M Mesbah; Samy M Saleh; Dina M Abo-Elmatty; Eman T Mehanna Journal: Biochem Genet Date: 2022-02-21 Impact factor: 1.890
Authors: Iris Reyhan; Olga S Zhukov; Robert J Lagier; Robert F Bridgforth; Gary J Williams; Joanna M Popov; Stanley J Naides; Andreas Reiff Journal: Pediatr Rheumatol Online J Date: 2021-02-16 Impact factor: 3.054