1. ¹Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
2. ²Department of Immunology, University of Toronto, Toronto, Ontario, Canada
3. ³The Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Toronto, Ontario, Canada
4. ⁴Department of Medicine, University of Toronto, Toronto, Ontario, Canada

Correspondence: Dr EN Fish, Toronto General Research Institute, University Health Network, Canadian Blood Services Building, Room 424, 67 College Street, Toronto, Ontario, Canada M5G 2M1. E-mail: en.fish@utoronto.ca

Received 9 January 2007; Revised 20 April 2007; Accepted 23 April 2007; Published online 14 June 2007.

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-, GPR64, POU3F3, peroxisome proliferative activated receptor- 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.