Rheumatology Advance Access originally published online on August 27, 2006
Rheumatology 2007 46(3):417-425; doi:10.1093/rheumatology/kel306
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Circulating cytokines in Norwegian patients with psoriatic arthritis determined by a multiplex cytokine array system
Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway, 1Oklahoma Medical Research Foundation, Oklahoma City, OK, USA, 2Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, 3Department of Rheumatology, Haukeland University Hospital, University of Bergen, Bergen, Norway, 4Division of Clinical Immunology, 3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary, 5Department of Pediatrics, University of Oklahoma College of Medicine, Oklahoma City, OK, USA and 6Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Correspondence to: P. Szodoray, MD, PhD, Broegelmann Research Laboratory, University of Bergen, Armauer Hansen Building N-5021 Bergen, Norway. E-mail: peter.szodoray{at}gades.uib.no
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Abstract |
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Objectives. Serum cytokines play an important role in the pathogenesis of psoriatic arthritis (PsA) by initiating and perpetuating various cellular and humoral autoimmune processes. The aim of this study was to describe a broad spectrum of T- and B-cell cytokines, growth factors and chemokines in patients with PsA and healthy individuals.
Methods. A novel protein array system, denoted as multiplex cytokine assay was utilized to measure simultaneously the levels of 23 circulating cytokines of patients with PsA and healthy individuals. Additionally, correlational clustering and discriminant function analysis (DFA), two multivariate, supervised analysis methods were employed to identify a subset of biomarkers in order to describe potential functional inter-relationships among these pathological cytokines and identify biomarkers with prognostic and diagnostic utility.
Results. Univariate analysis demonstrated that serum levels of a complex set of immune and inflammatory modulating cytokines are significantly up-regulated in patients with PsA relative to unaffected controls including interleukin (IL)-10, IL-13, interferen (IFN)-
, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), fibroblast growth factor [CCL3 macrophage inflammatory protein (MIP)-1], CCL4 (MIP-1ß) and CCL11 (Eotaxin), while granulocyte-colony stimulating factor was significantly reduced in PsA patients. Correlational clustering was able to discriminate among, and hence subclassify, patients with varying levels of disease activity, which may prove useful in guiding therapy in these apparently phenotypically distinct disease subsets. DFA identified EGF, IFN-, VEGF, CCL3 (MIP-1) and IL-12p40 as analytes with the strongest discriminatory power among various PsA patients and controls.
Conclusions. Our findings suggest that these factors modulate PsA pathology and the articular involvement in a synergistic manner. Identifying factors could be used in the development of clinical diagnostic tests, which are valuable to guide evidence-based diagnosis and disease management of PsA.
KEY WORDS: Psoriatic arthritis, Circulating cytokines, Hierarchical clustering, Discriminant function analysis, Disease activity, Multiplex cytokine array system
*Contributed equally to this work.
Submitted 3 February 2006;
revised version accepted 21 June 2006.
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