Rheumatology Advance Access originally published online on April 25, 2006
Rheumatology 2006 45(12):1466-1476; doi:10.1093/rheumatology/kel095
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A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients with rheumatoid arthritis
1Microarray Research Facility, Arthritis and Immunology Research Program and 2Molecular Immunogenetics Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA and 3Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway.
Correspondence to: Peter Szodoray MD, PhD, Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Armauer Hansen Bldg, N-5021 Bergen, Norway. E-mail: peter.szodoray{at}gades.uib.no
Objective. While rheumatoid arthritis (RA) is considered a prototypical autoimmune disease, the specific roles of B-cells in RA pathogenesis is not fully delineated.
Methods. We performed microarray expression profiling of peripheral blood B-cells from RA patients and controls. Data were analysed using differential gene expression analysis and ‘gene networking’ analysis (characterizing clusters of functionally inter-relelated genes) to identify both regulatory genes and the pathways in which they participate. Results were confirmed by quantitative real-time polymerase chain reaction and by measuring the levels of 10 serum cytokines involved in the pathways identified.
Results. Genes regulating and effecting the cell-cycle, proliferation, apoptosis, autoimmunity, cytokine networks, angiogenesis and neuro-immune regulation were differentially expressed in RA B-cells. Moreover, the serum levels of several soluble factors that modulate these pathways, including IL-1ß, IL-5, IL-6, IL-10, IL-12p40, IL-17 and VEGF were significantly increased in this cohort of RA patients.
Conclusions. These results outline aspects of the multifaceted role B-cells play in RA pathogenesis in which immune dysregulation in RA modulates B-cell biology and thereby contributes to the induction and perpetuation of a pathogenic humoral immune response.
KEY WORDS: Rheumatoid arthritis, Peripheral blood B-cells, Microarray, Multiplex cytokine assay.
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