Expression of a pathogen-response program in peripheral blood cells defines a subgroup of rheumatoid arthritis patients.
Rheumatoid arthritis (RA) is a heterogeneous disease with unknown etiology. Here we aimed to distinguish RA subtypes based on peripheral blood (PB) gene expression profiles in comparison with a pathogen-response transcriptional program. PB was obtained from 35 RA patients and 15 healthy individuals. For expression profiling we used DNA microarrays. A combined cluster analysis of RA and control samples together with samples from a viral infection model revealed that the gene expression profile of a subgroup of RA patients (RA(A)) was reminiscent to that of poxvirus-infected macaques. Statistical analysis, followed by Gene Ontology analysis of the RA(A) patients confirmed that these patients form a distinct group, with activation of several host defense mechanisms that resemble a common host-pathogen response. Analysis of the promoter region of genes that were overexpressed in the RA(A) patients, revealed an enrichment of transcription factor binding sites for NF kappaB and interferon-activated transcription factors. Moreover, this subgroup of RA patients expressed significantly increased titers of anti-cyclic citrullinated peptide antibodies. We conclude that activation of a host-pathogen response defines a subgroup of RA patients characterized by increased autoreactivity against citrullinated proteins.
van der Pouw Kraan
T C T M
TC
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. t.vanderpouwkraan@vumc.nl
van Baarsen
L G M
LG
Wijbrandts
C A
CA
Voskuyl
A E
AE
Rustenburg
F
F
Baggen
J M
JM
Dijkmans
B A C
BA
Tak
P P
PP
Verweij
C L
CL
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000145:classification* / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005814:Genes, Viral; D006790:Host-Parasite Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008251:Macaca / Q000821:virology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012899:Smallpox; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D014157:Transcription Factors