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Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity

Genes & Immunity volume 8, pages 480–491 (2007)Cite this article

Abstract

Gene expression profiling of rheumatoid arthritis (RA) and osteoarthritis (OA) joint tissue samples provides a unique insight into the gene signatures involved in disease development and progression. Fibroblast-like synovial (FLS) cells were obtained from RA, OA and control trauma joint tissues (non-RA, non-OA) and RNA was analyzed by Affymetrix microarray. Thirty-four genes specific to RA and OA FLS cells were identified (P<0.05). HOXD10, HOXD11, HOXD13, CCL8 and LIM homeobox 2 were highly and exclusively expressed in RA and CLU, sarcoglycan-γ, GPR64, POU3F3, peroxisome proliferative activated receptor-γ and tripartite motif-containing 2 were expressed only in OA. The data also revealed expression heterogeneity for patients with the same disease. To address disease heterogeneity in RA FLS cells, we examined the effects of clinical disease parameters (Health Assessment Questionnaire (HAQ) score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF)) and drug therapies (methotrexate/prednisone) on RA FLS cell gene expression. Eight specific and unique correlations were identified: human leukocyte antigen (HLA)-DQA2 with HAQ score; Clec12A with RF; MAB21L2, SIAT7E, HAPLN1 and BAIAP2L1 with CRP level; RGMB and OSAP with ESR. Signature RA FLS cell gene expression profiles may provide insights into disease pathogenesis and have utility in diagnosis, prognosis and drug responsiveness.

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Acknowledgements

We gratefully acknowledge Susan Dubbin for coordinating patient sample collection and Mileidys Alvarez and Thomas Burian for their technical assistance. The work was supported by grants from Genome Canada, the McLaughlin Centre for Molecular Medicine, Toronto and The Arthritis Society of Canada.

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Authors and Affiliations

  1. Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada

    C L Galligan, E Baig & E N Fish

  2. Department of Immunology, University of Toronto, Toronto, Ontario, Canada

    C L Galligan, E Baig & E N Fish

  3. The Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Toronto, Ontario, Canada

    V Bykerk & E C Keystone

  4. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    V Bykerk & E C Keystone

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  1. C L Galligan
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Correspondence to E N Fish.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Galligan, C., Baig, E., Bykerk, V. et al. Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity. Genes Immun 8, 480–491 (2007). https://doi.org/10.1038/sj.gene.6364400

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