Drs. Nzeusseu Toukap and Galant contributed equally to this work.
Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus
Article first published online: 27 APR 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 56, Issue 5, pages 1579–1588, May 2007
How to Cite
Toukap, A. N., Galant, C., Theate, I., Maudoux, A. L., Lories, R. J. U., Houssiau, F. A. and Lauwerys, B. R. (2007), Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus. Arthritis & Rheumatism, 56: 1579–1588. doi: 10.1002/art.22578
- Issue published online: 27 APR 2007
- Article first published online: 27 APR 2007
- Manuscript Accepted: 29 JAN 2007
- Manuscript Received: 31 OCT 2006
- Fonds de la Recherche Scientifique et Médicale, Belgium
- Fonds Spécial de Recherche (Communauté française de Belgique)
- Ministère des Affaires Sociales, de la Santé Publique et de l'Environnement, Belgium
Synovitis is a common feature of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but the pattern of joint involvement differs in each disease. This study was undertaken to investigate the global gene expression profiles in synovial biopsy tissue from the swollen knees of untreated SLE patients (n = 6), RA patients (n = 7), and osteoarthritis (OA) patients (n = 6).
Synovial biopsy samples were obtained from the affected knees of patients in the 3 groups by needle arthroscopy. Half of the material was used for extraction of total RNA, amplification of complementary RNA, and high-density oligonucleotide spotted hybridization arrays. On the remaining tissue samples, real-time reverse transcription–polymerase chain reaction (RT-PCR) and immunohistochemical experiments were performed to confirm the microarray data.
SLE synovial biopsy tissue displayed a significant down-regulation of genes involved in extracellular matrix (ECM) homeostasis and a significant up-regulation of interferon-inducible (IFI) genes. Real-time RT-PCR experiments confirmed the up-regulation of selected IFI genes (IFI27, IFI44, and IFI44L) in the SLE synovial tissue. Immunohistochemical analyses showed that 3 molecules involved in ECM regulation, chondroitin sulfate proteoglycan 2, latent transforming growth factor β binding protein 2, and fibroblast activation protein α, were significantly down-regulated in SLE synovium. In contrast, immunostaining for IFI27, Toll-like receptor 4, and STAT-1 resulted in higher quantitative scores in SLE synovial tissue, which could be attributed to the fact that the RA samples had a large population of inflammatory cell infiltrates that were negative for these markers.
Arthritis in SLE has a very distinct molecular signature as compared with that in OA and RA, characterized by up-regulation of IFI genes and down-regulation of genes involved in ECM homeostasis.