A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients with rheumatoid arthritis

Peter Szodoray, P. Alex, M. B. Frank, M. Turner, S. Turner, N. Knowlton, C. Cadwell, I. Dozmorov, Y. Tang, P. C. Wilson, R. Jonsson, M. Centola

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Abstract

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-1β, 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.

Original languageEnglish (US)
Pages (from-to)1466-1476
Number of pages11
JournalRheumatology
Volume45
Issue number12
DOIs
StatePublished - Dec 1 2006

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Keywords

  • Microarray
  • Multiplex cytokine assay
  • Peripheral blood B-cells
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

Szodoray, P., Alex, P., Frank, M. B., Turner, M., Turner, S., Knowlton, N., Cadwell, C., Dozmorov, I., Tang, Y., Wilson, P. C., Jonsson, R., & Centola, M. (2006). A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients with rheumatoid arthritis. Rheumatology, 45(12), 1466-1476. https://doi.org/10.1093/rheumatology/kel095