Expression of a pathogen-response program in peripheral blood cells defines a subgroup of rheumatoid arthritis patients

T. C. T. M. van der Pouw Kraan, L. G. M. van Baarsen, C. A. Wijbrandts, A. E. Voskuyl, F. Rustenburg, J. M. Baggen, B. A. C. Dijkmans, P. P. Tak, C. L. Verweij

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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
Original languageEnglish
Pages (from-to)16-22
JournalGenes and immunity
Issue number1
Publication statusPublished - 2008

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