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Expression of a pathogen-response program in peripheral blood cells defines a subgroup of Rheumatoid Arthritis patients

2007; Springer Nature; Volume: 9; Issue: 1 Linguagem: Inglês

10.1038/sj.gene.6364438

1476-5470

Tineke C. T. M. van der Pouw Kraan, Lisa G. M. van Baarsen, Carla A. Wijbrandts, Alexandre E. Voskuyl, François Rustenburg, Josefien M. Baggen, Ben A. C. Dijkmans, Paul P. Tak, C L Verweij,

Herpesvirus Infections and Treatments

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 (RAA) was reminiscent to that of poxvirus-infected macaques. Statistical analysis, followed by Gene Ontology analysis of the RAA 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 RAA patients, revealed an enrichment of transcription factor binding sites for NFκB 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.