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Defect in A20 gene expression causes rheumatoid arthritis
Date:8/16/2011

Researchers from VIB (Flanders Institute for Biotechnology) and Ghent University have shown that a defective gene can contribute to the onset of rheumatoid arthritis, an often-crippling inflammation of the joints that afflicts about 1% of the world's population. Until now, the underlying molecular mechanism of the disease was largely unclear. In the study, published in Nature Genetics, the researchers demonstrate that a cell-specific defect in the expression of the A20 gene (TNFAIP3) can contribute to the development of rheumatoid arthritis in mice, thereby identifying A20 as a possible target for the generation of new drugs.

Rheumatoid arthritis (RA)

RA is a chronic progressive joint disease that starts with the inflammation of the synovial membrane and soft tissues around the joints, but often spreads to cartilage and bones. The disease is very painful for the patient. Although the cause of rheumatoid arthritis remains unknown, autoimmunity plays a crucial role. Currently, the progression of the disease can be slowed down, but RA cannot be cured.

Protein A20

A20 is an intracellular negative regulator of the NF-kB transcription factor, which plays a key role in the generation of the inflammatory response. Excessive activation of NF-kB can lead to a whole range of inflammatory diseases, including arthritis. The research group of Rudi Beyaert investigates the molecular mechanisms that control NF-kB activation and earlier in vitro research already indicated a key role for A20. Moreover, genome-wide association studies in humans recently suggested that defects in A20 could contribute to several autoimmune diseases, including RA.

Mouse Model for RA

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-supervi
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Contact: Joris Gansemans
joris.gansemans@vib.be
329-244-6611
VIB (the Flanders Institute for Biotechnology)
Source:Eurekalert

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