Open Access Highly Accessed Research article

Variability in synovial inflammation in rheumatoid arthritis investigated by microarray technology

Johan Lindberg1, Erik af Klint2, Ann-Kristin Ulfgren2, André Stark3, Tove Andersson1, Peter Nilsson1, Lars Klareskog2 and Joakim Lundeberg1*

Author Affiliations

1 Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology, S-106 91 Stockholm, Sweden

2 Department of Rheumatology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden

3 Department of Orthopedics, Karolinska University Hospital, 171 76 Stockholm, Sweden

For all author emails, please log on.

Arthritis Research & Therapy 2006, 8:R47  doi:10.1186/ar1903

Published: 16 February 2006

Abstract

In recent years microarray technology has been used increasingly to acquire knowledge about the pathogenic processes involved in rheumatoid arthritis. The present study investigated variations in gene expression in synovial tissues within and between patients with rheumatoid arthritis. This was done by applying microarray technology on multiple synovial biopsies obtained from the same knee joints. In this way the relative levels of intra-patient and inter-patient variation could be assessed. The biopsies were obtained from 13 different patients: 7 by orthopedic surgery and 6 by rheumatic arthroscopy. The data show that levels of heterogeneity varied substantially between the biopsies, because the number of genes found to be differentially expressed between pairs of biopsies from the same knee ranged from 6 to 2,133. Both arthroscopic and orthopedic biopsies were examined, allowing us to compare the two sampling methods. We found that the average number of differentially expressed genes between biopsies from the same patient was about three times larger in orthopedic than in arthroscopic biopsies. Using a parallel analysis of the tissues by immunohistochemistry, we also identified orthopedic biopsies that were unsuitable for gene expression analysis of synovial inflammation due to sampling of non-inflamed parts of the tissue. Removing these biopsies reduced the average number of differentially expressed genes between the orthopedic biopsies from 455 to 171, in comparison with 143 for the arthroscopic biopsies. Hierarchical clustering analysis showed that the remaining orthopedic and arthroscopic biopsies had gene expression signatures that were unique for each patient, apparently reflecting patient variation rather than tissue heterogeneity. Subsets of genes found to vary between biopsies were investigated for overrepresentation of biological processes by using gene ontology. This revealed representative 'themes' likely to vary between synovial biopsies affected by inflammatory disease.