Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Serum 14-3-3: A Rheumatoid Arthritis Biomarker.
Maksymowych1, Walter P., Landewe2, Robert, van der Heijde3, Désirée, Tak4, Paul-Peter, Marotta5, Anthony
University of Alberta, Edmonton, AB
Academic Medical Center, Amsterdam, Netherlands
Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands
Professor of Medicine/ Director, Division of Clinical Immunology and Rheumatology, Amsterdam, Netherlands
Augurex Life Sciences Corp, North Vancouver, BC
Intracellular 14-3-3 proteins represent a family of ubiquitously expressed chaperonins consisting of seven highly conserved isoforms. Only one isoform, 14-3-3h, is significantly detected in arthritis and is differentially expressed extracellularly in rheumatoid arthritis (RA) compared to healthy controls and may have independent diagnostic utility from other RA serological markers. This study compared 14-3-3h serum expression in patients with RA versus ankylosing spondylitis (AS) and in autoimmune (AI) disease controls.
Levels of serum 14-3-3h were measured in 267 patients, 135 RA, 67 AS and 65 AI controls, using an investigational-grade 14-3-3h ELISA to evaluate the biomarker's differential expression in RA. Mean (SD) age for RA patients (72% female) was 59.4 (12.7) and 41.9 (13.2) for AS patients (25% female). Diagnosis was according to ARA 1987 and modified New York criteria, respectively. RA patients were on standard DMARDs but naïve of biological therapy. AI controls included 10 each of psoriasis, ulcerative colitis, type 1 diabetes, SLE, Crohn's, and 5 each of primary Sjogren's, scleroderma, and multiple sclerosis. Two-tailed t-tests and Mann-Whitney u-tests were used to compare group differences in serum concentrations. ROC curves were generated and diagnostic utility estimated by area under the curve and likelihood ratios (LR) for various 14-3-3h serum concentration cut-offs.
14-3-3h mean and medium serum concentrations were significantly higher in RA subjects at 4.58 and 1.12ng/ml, respectively compared to AS (0.14 and 0.02ng/ml; p <0.0001) and AI (0.21 and 0.03ng/ml; p <0.0001). The area under the ROC curve for RA versus AS was 0.86 (95%CI 0.81 to 0.91; p <0.0001) and RA versus AI was 0.85 (95%CI 0.79 to 0.90; p <0.0001). There were no differences in mean or median 14-3-3h serum concentrations between the AS and AI groups. A best cut-off level of 0.23ng/ml provides a positive likelihood ratio (LR+) of 5 and a negative likelihood ratio (LR-) of 0.30 for RA versus AS. For 14-3-3h levels above 0.72 and 0.88ng/ml, LR+ was 10 and 36, and LR- was 0.40 and 0.47, respectively.
Differential expression of 14-3-3h in RA versus AS and its absence in a wide range of other autoimmune disorders supports its utility as a diagnostic marker in RA.
To cite this abstract, please use the following information:
Maksymowych, Walter P., Landewe, Robert, van der Heijde, Désirée, Tak, Paul-Peter, Marotta, Anthony; Serum 14-3-3: A Rheumatoid Arthritis Biomarker. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :358