A Genome-Scale Assessment of Peripheral Blood B-cell Molecular Homeostasis in Patients With Rheumatoid Arthritis

Rheumatology (Oxford). 2006 Dec;45(12):1466-76. doi: 10.1093/rheumatology/kel095. Epub 2006 Apr 25.

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-1beta, 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cohort Studies
  • Cytokines / blood
  • Female
  • Gene Expression / immunology
  • Gene Expression Profiling / methods
  • Gene Regulatory Networks
  • Genome
  • Homeostasis / genetics
  • Homeostasis / immunology
  • Humans
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / methods
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Cytokines
  • Inflammation Mediators
  • Vascular Endothelial Growth Factor A