Variability in synovial inflammation in rheumatoid arthritis investigated by microarray technology

Rheumatoid arthritis (RA) is a common chronic inflammatory disease, so far defined by a set of criteria [1] rather than by a knowledge of the underlying molecular pathogenesis. Substantial efforts have been made to characterize the synovial inflammation in RA, and during these studies it has become evident that there is a large variability in cell content and in protein expression, both within single joints and between patients with RA [2-7]. This variation also exists at the gene expression level [8]. Microarray (MA) technology allows the expression of thousands of genes to be monitored simultaneously and can thus increase the understanding of the complicated molecular processes of joint inflammation in more detail than has been possible with immunohistochemistry and related techniques [9-14]. Recently reviewed [15], MA has been used to acquire knowledge about RA in various experimental systems with the use of both cell cultures [16-22] and biopsies [23-30] obtained from the synovium. So far, MA has been used to investigate tissue heterogeneity between synovial biopsies obtained from different patients in both juvenile RA [23] and long-standing RA [25,30]. Tsubaki and colleagues [23] used laser capture microdissection on biopsies retrieved by rheumatic arthroscopy from patients with juvenile RA to characterize proliferative lesions in the synovial lining. Two subgroups were discovered; one had a gene expression profile similar to that of long-standing RA. Van der Pouw Kraan and colleagues [25,30] used MA to investigate heterogeneity between synovial biopsies obtained by orthopedic surgery from different patients. In both of these studies, at least two different gene expression profiles were observed, which were suggested to correspond to high and low inflammatory status.These and other studies therefore suggest that the MA technique might indeed be able to discern variable molecular features of the joint inflammation that would be both biologically and clinically m