Researchers continue to search for genetic clues into rheumatoid arthritis (RA), a chronic inflammatory joint disease.
While its specific cause is not yet known, RA has been linked to an inherited susceptibility. Interestingly, despite its strong genetic component, RA's occurrence among siblings seems to be random.
In the quest to identify disease-specific gene expression profiles in patients with RA, researchers at the University of Michigan Medical Center turned to an ideal population: genetically identical, disease-discordant twins. The July issue of Arthritis & Rheumatism highlights the results of their state-of-the-art genetic analysis.
Increasing evidence over the past several years indicates that B-lymphocytes play a central role in RA's development. In this study, microarray analysis was applied to lymphoblastoid B cell lines (LCLs) from 11 pairs of monozygotic twins, all with one healthy and one RA-affected twin. A revolutionary DNA technology, microarray can be used to not only compare gene expression in two different tissue samples, but to examine the expression of thousands of genes at once. The researchers extracted complementary DNA from the cells of every twin, labelled samples with fluorescent dye to distinguish RA cells from disease-free cells, and hybridized each on a 20,000-gene chip. Then, using immunohistochemistry and real-time polymerase chain reaction, they confirmed the expression of the most significantly over-expressed genes in synovial tissues. In addition, they compared gene expression in synovial tissue of the RA patients with gene expression in synovial tissue of patients with osteoarthritis (OA).