A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients with rheumatoid arthritis.
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.
Szodoray
P
P
Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Armauer Hansen Bldg, N-5021 Bergen, Norway. peter.szodoray@gades.uib.no
Alex
P
P
Frank
M B
MB
Turner
M
M
Turner
S
S
Knowlton
N
N
Cadwell
C
C
Dozmorov
I
I
Tang
Y
Y
Wilson
P C
PC
Jonsson
R
R
Centola
M
M
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D016678:Genome; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D016207:Cytokines; D018836:Inflammation Mediators; D042461:Vascular Endothelial Growth Factor A