London: A defective gene, can contribute to the onset of rheumatoid arthritis (RA), a new study has shown.
In their study, researchers from VIB (Flanders Institute for Biotechnology) and Ghent University demonstrated that a cell-specific defect in the expression of the A20 gene could contribute to the development of rheumatoid arthritis in mice, thereby identifying A20 as a possible target for the generation of new drugs.
A20 is a protein, which plays a key role in the generation of the inflammatory response.
VIB researchers led by Geert van Loo and Rudi Beyaert at Ghent University have developed mice with myeloid cells incapable of producing A20.
In collaboration with Dirk Elewaut, rheumatologist at Ghent University Hospital (Ghent University), who co-supervised the research, they found that these mice had elevated levels of pro-inflammatory cytokines in their blood and joints, and spontaneously developed RA with severe inflammation and osteoporosis.
Interestingly, the arthritis in this mouse model was not dependent on TNF, a cytokine that normally plays an essential role in many inflammatory diseases including RA.
The study confirms the crucial role of A20 in the control of inflammatory responses and shows that a defect in A20 in myeloid cells can give rise to RA that is not responsive to anti-TNF treatment.
From a therapeutic perspective, this is a very important finding, since anti-TNF therapy fails in 30 percent of RA patients.
The study has been published in Nature Genetics.