Synovial gene signatures associated with later RA onset
medwireNews: Researchers have found molecular changes appearing in the synovial tissue that precede rheumatoid arthritis (RA) development and may tell us more about the pathogenesis of the disease and treatment targets.
The team recruited 67 individuals who were positive for the RA-associated immunoglobulin M rheumatoid factor or anti-citrullinated protein antibody, of whom 17 developed RA over a median follow-up of 4 years.
At enrollment into the study, the participants underwent a mini-arthroscopic synovial biopsy of the knee joint and the samples underwent thorough analysis in the laboratory, including molecular analysis, DNA chips, and microscopy studies.
As reported at the EULAR 2018 meeting in Amsterdam, the Netherlands, this showed a set of about 30 genes that characterized the at-risk individuals into two groups according to high and low gene activity. The individuals who went on to develop RA largely clustered together in one group, noted researcher Lisa Van Baarsen (Academic Medical Center, Amsterdam).
Further analysis of some of the higher activity genes in this group at the protein level showed activation of tissue-resident stromal cells and high expression of molecules involved in the attraction and migration of immune cells.
By contrast, analysis of the low activity genes showed that one of the pathways involved was lower lipid metabolism in the synovial tissue, which Van Baarsen said, “really deserves future research.”
She concluded: “Before the onset of disease we do find molecular changes in the synovial tissue reflected by a higher activity of immune response pathways and a lower activity of lipid metabolism.
“This kind of tissue analysis will tell us more about pathogenesis and what kind of drug targets we should aim for.”
By Lucy Piper
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