Researchers have found that a defective gene can contribute to the onset of rheumatoid arthritis, a crippling inflammation of the joints that affect about 1 percent of the world's population.

Until now, the underlying molecular mechanism of the disease was largely unclear. Researchers from VIB (Flanders Institute for Biotechnology) and Ghent University in a study published in the journal Nature Genetics, demonstrated that a cell-specific defect in the expression of the A20 gene (TNFAIP3) can contribute to the A20 gene as a possible target for the next generation of new drugs.

The protein 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 expression of NF-kB can lead to much inflammatory disease.

Rheumatoid Arthritis (RA) is a form of arthritis that causes pain, swelling, stiffness and loss of function in joints. The disease can last for a short time, or symptoms might come and go. The severe form can last a lifetime. An estimated 1.293 million adults aged 18 and older (0.6%) has RA in the US.

Rudi Beyaert investigated the molecular mechanism that control NF-kB activation and found A20 to play a key role, others studies have suggested that A20 could contribute to several autoimmune diseases including RA.

Researchers genetically developed mice with myeloid cells incapable of producing A20. 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.

The study confirms the crucial role of A20 in controlling inflammatory response and show that defect in a20 in myeloid cells can give rise to RA.