Featured Research

from universities, journals, and other organizations

Defect in A20 gene expression can contribute to onset of rheumatoid arthritis

Date:
August 16, 2011
Source:
VIB (the Flanders Institute for Biotechnology)
Summary:
Researchers in Belgium have shown that a defective gene can contribute to the onset of rheumatoid arthritis, an often-crippling inflammation of the joints that afflicts about one percent of the world's population.

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.

Related Articles


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-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. On the other hand, they were able to demonstrate a role for IL-6 and Toll-like receptor 4 (TLR4).

Impact

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% of RA patients. The A20-deficient mice are therefore an interesting new mouse model for the study of new therapeutics for RA.

In collaboration with Bart Lambrecht (Ghent University Hospital, Ghent University), the VIB researchers recently demonstrated that mice lacking A20 in dendritic cells, a specific myeloid cell type, also develop an autoimmune pathology that in this case shows more similarities with systemic lupus erythematosus, which is characterized by acute and chronic inflammation of various tissues of the human body (Kool et al., Immunity 2011).


Story Source:

The above story is based on materials provided by VIB (the Flanders Institute for Biotechnology). Note: Materials may be edited for content and length.


Journal References:

  1. Mourad Matmati, Peggy Jacques, Jonathan Maelfait, Eveline Verheugen, Mirjam Kool, Mozes Sze, Lies Geboes, Els Louagie, Conor Mc Guire, Lars Vereecke, Yuanyuan Chu, Louis Boon, Steven Staelens, Patrick Matthys, Bart N Lambrecht, Marc Schmidt-Supprian, Manolis Pasparakis, Dirk Elewaut, Rudi Beyaert, Geert van Loo. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nature Genetics, 2011; DOI: 10.1038/ng.874
  2. Mirjam Kool, Geert van Loo, Wim Waelput, Sofie De Prijck, Femke Muskens, Mozes Sze, Jens van Praet, Filipe Branco-Madeira, Sophie Janssens, Boris Reizis, Dirk Elewaut, Rudi Beyaert, Hamida Hammad, Bart N. Lambrecht. The Ubiquitin-Editing Protein A20 Prevents Dendritic Cell Activation, Recognition of Apoptotic Cells, and Systemic Autoimmunity. Immunity, 2011; 35 (1): 82 DOI: 10.1016/j.immuni.2011.05.013

Cite This Page:

VIB (the Flanders Institute for Biotechnology). "Defect in A20 gene expression can contribute to onset of rheumatoid arthritis." ScienceDaily. ScienceDaily, 16 August 2011. <www.sciencedaily.com/releases/2011/08/110816111303.htm>.
VIB (the Flanders Institute for Biotechnology). (2011, August 16). Defect in A20 gene expression can contribute to onset of rheumatoid arthritis. ScienceDaily. Retrieved March 28, 2015 from www.sciencedaily.com/releases/2011/08/110816111303.htm
VIB (the Flanders Institute for Biotechnology). "Defect in A20 gene expression can contribute to onset of rheumatoid arthritis." ScienceDaily. www.sciencedaily.com/releases/2011/08/110816111303.htm (accessed March 28, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, March 28, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) — A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
Powered by NewsLook.com
House Ready to Pass Medicare Doc Bill

House Ready to Pass Medicare Doc Bill

AP (Mar. 26, 2015) — In rare bipartisan harmony, congressional leaders pushed a $214 billion bill permanently blocking physician Medicare cuts toward House passage Thursday, moving lawmakers closer to resolving a problem that has plagued them for years. (March 26) Video provided by AP
Powered by NewsLook.com
What's Different About This Latest Ebola Vaccine

What's Different About This Latest Ebola Vaccine

Newsy (Mar. 26, 2015) — A whole virus Ebola vaccine has been shown to protect monkeys exposed to the virus. Here&apos;s what&apos;s different about this vaccine. Video provided by Newsy
Powered by NewsLook.com
HIV Outbreak Prompts Public Health Emergency In Indiana

HIV Outbreak Prompts Public Health Emergency In Indiana

Newsy (Mar. 26, 2015) — Indiana Gov. Mike Pence says he will bring additional state resources to help stop the epidemic. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins