Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients.
BACKGROUND
Rheumatoid arthritis (RA) is a heterogeneous disease with unknown cause.


OBJECTIVE
To identify peripheral blood (PB) gene expression profiles that may distinguish RA subtypes.


METHODS
Large-scale expression profiling by cDNA microarrays was performed on PB from 35 patients and 15 healthy individuals. Differential gene expression was analysed by significance analysis of microarrays (SAM), followed by gene ontology analysis of the significant genes. Gene set enrichment analysis was applied to identify pathways relevant to disease.


RESULTS
A substantially raised expression of a spectrum of genes involved in immune defence was found in the PB of patients with RA compared with healthy individuals. SAM analysis revealed a highly significant elevated expression of interferon (IFN) type I regulated genes in patients with RA compared with healthy individuals, which was confirmed by gene ontology and pathway analysis, suggesting that this pathway was activated systemically in RA. A quantitative analysis revealed that increased expression of IFN-response genes was characteristic of approximately half of the patients (IFN(high) patients). Application of pathway analysis revealed that the IFN(high) group was largely different from the controls, with evidence for upregulated pathways involved in coagulation and complement cascades, and fatty acid metabolism, while the IFN(low) group was similar to the controls.


CONCLUSIONS
The IFN type I signature defines a subgroup of patients with RA, with a distinct biomolecular phenotype, characterised by increased activity of the innate defence system, coagulation and complement cascades, and fatty acid metabolism.
van der Pouw Kraan
T C T M
TC
Department of Molecular and Cellular Biology & Immunology, VU Medical Centre, J295, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
Wijbrandts
C A
CA
van Baarsen
L G M
LG
Voskuyl
A E
AE
Rustenburg
F
F
Baggen
J M
JM
Ibrahim
S M
SM
Fero
M
M
Dijkmans
B A C
BA
Tak
P P
PP
Verweij
C L
CL
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001777:Blood Coagulation / Q000235:genetics; D003167:Complement Activation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation
D007370:Interferon Type I