Research ArticleArticle
Open Access
Serum 14-3-3η is a Novel Marker that Complements Current Serological Measurements to Enhance Detection of Patients with Rheumatoid Arthritis
Walter P. Maksymowych, Stanley J. Naides, Vivian Bykerk, Katherine A. Siminovitch, Dirkjan van Schaardenburg, Maarten Boers, Robert Landewé, Désirée van der Heijde, Paul-P. Tak, Mark C. Genovese, Michael E. Weinblatt, Edward Keystone, Olga S. Zhukov, Rania W. Abolhosn, Joanna M. Popov, Karin Britsemmer, Arno W. van Kuijk and Anthony Marotta
The Journal of Rheumatology August 2014, jrheum.131446; DOI: https://doi.org/10.3899/jrheum.131446
Walter P. Maksymowych
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Stanley J. Naides
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Vivian Bykerk
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Katherine A. Siminovitch
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Dirkjan van Schaardenburg
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Maarten Boers
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Robert Landewé
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Désirée van der Heijde
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Paul-P. Tak
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Mark C. Genovese
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Michael E. Weinblatt
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Edward Keystone
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Olga S. Zhukov
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Rania W. Abolhosn
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Joanna M. Popov
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Karin Britsemmer
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Arno W. van Kuijk
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Anthony Marotta
From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women’s Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK. Supported by Augurex Life Sciences Corp., North Vancouver, British Columbia, Canada. W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women’s Hospital; E. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp. Address correspondence to Dr. W.P. Maksymowych, Professor of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca. Accepted for publication June 10, 2014.
Abstract
Objective Serum 14-3-3η is a novel joint-derived proinflammatory mediator implicated in the pathogenesis of rheumatoid arthritis (RA). In our study, we assessed the diagnostic utility of 14-3-3η and its association with standard clinical and serological measures.
Methods A quantitative ELISA was used to assess 14-3-3η levels. Early (n = 99) and established patients with RA (n = 135) were compared to all controls (n = 385), including healthy subjects (n = 189). The sensitivity, specificity, positive and negative predictive values of 14-3-3η, and the likelihood ratios (LR) for RA were determined through receiver-operator curve analysis. The incremental value of adding 14-3-3η to anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in diagnosing early and established RA was assessed.
Results Serum 14-3-3η differentiated established patients with RA from healthy individuals and all controls (p < 0.0001). A serum 14-3-3η cutoff of ≥ 0.19 ng/ml delivered a sensitivity and specificity of 77% and 93%, respectively, with corresponding LR positivity of 10.4. At this cutoff in early RA, 64% of patients with early RA were positive for 14-3-3η, with a corresponding specificity of 93% (LR+ of 8.6), while 59% and 57% were positive for ACPA or RF, respectively. When ACPA, RF, and 14-3-3η positivity were used in combination, 77 of the 99 patients (78%) with early RA were positive for any 1 of the 3 markers. Serum 14-3-3η did not correlate with C-reactive protein, erythrocyte sedimentation rate, or Disease Activity Score, but patients who were 14-3-3η-positive had significantly worse disease.
Conclusion Serum 14-3-3η is a novel RA mechanistic marker that is highly specific, associated with worse disease, and complements current markers, enabling a more accurate diagnosis of RA.
In this issue
The Journal of Rheumatology
Vol. 47, Issue 8
1 Aug 2020
Serum 14-3-3η is a Novel Marker that Complements Current Serological Measurements to Enhance Detection of Patients with Rheumatoid Arthritis
Walter P. Maksymowych, Stanley J. Naides, Vivian Bykerk, Katherine A. Siminovitch, Dirkjan van Schaardenburg, Maarten Boers, Robert Landewé, Désirée van der Heijde, Paul-P. Tak, Mark C. Genovese, Michael E. Weinblatt, Edward Keystone, Olga S. Zhukov, Rania W. Abolhosn, Joanna M. Popov, Karin Britsemmer, Arno W. van Kuijk, Anthony Marotta
The Journal of Rheumatology Aug 2014, jrheum.131446; DOI: 10.3899/jrheum.131446
Serum 14-3-3η is a Novel Marker that Complements Current Serological Measurements to Enhance Detection of Patients with Rheumatoid Arthritis
Walter P. Maksymowych, Stanley J. Naides, Vivian Bykerk, Katherine A. Siminovitch, Dirkjan van Schaardenburg, Maarten Boers, Robert Landewé, Désirée van der Heijde, Paul-P. Tak, Mark C. Genovese, Michael E. Weinblatt, Edward Keystone, Olga S. Zhukov, Rania W. Abolhosn, Joanna M. Popov, Karin Britsemmer, Arno W. van Kuijk, Anthony Marotta
The Journal of Rheumatology Aug 2014, jrheum.131446; DOI: 10.3899/jrheum.131446
