Navigation Links
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-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).


'/>"/>

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

Related biology technology :

1. Cardica Receives $1 Million Milestone Payment From Cook Medical for Development of Heart Defect Closure Device
2. Worlds First Low Radiocarbon Food May Reduce Risks of Cancer and Birth Defects, and Possibly Even Slow the Aging Process
3. Asbestos, Pharmaceutical Liability, Construction Defects, Nanotech: Covered by Targeted CLE Teleconferences
4. Watching crystals grow provides clues to making smoother, defect-free thin films
5. Nanotube defects equal better energy and storage systems
6. Repligen Files Investigational New Drug Application with FDA for First Drug Targeting the Core Genetic Defect of Friedreichs Ataxia
7. Supreme Court Amicus Brief Filed Opposing Lawsuit Protection for Manufacturers of Defectively Designed Vaccines
8. Graphenes strength lies in its defects
9. Model Predicts a Drugs Likelihood of Causing Birth Defects
10. Defect in graphene may present bouquet of possibilities
11. Xceed Ziplex(R) System for Automated Gene-Expression Analysis Wins 2008 R&D 100 Award
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... CA (PRWEB) , ... June 27, 2016 , ... ... for clinical trials, announced today the Clinical Reach Virtual Patient Encounter CONSULT ... care circle with the physician and clinical trial team. , Using the CONSULT module, ...
(Date:6/27/2016)... June 27, 2016   Ginkgo Bioworks , a ... engineering, was today awarded as one of the ... the world,s most innovative companies. Ginkgo Bioworks is ... the real world in the nutrition, health and ... directly with customers including Fortune 500 companies to ...
(Date:6/24/2016)... ... June 24, 2016 , ... Researchers at the Universita Politecnica delle Marche ... with peritoneal or pleural mesothelioma. Their findings are the subject of a new article ... Diagnostic biomarkers are signposts in the blood, lung fluid or tissue of mesothelioma patients ...
(Date:6/23/2016)... June 23, 2016 /PRNewswire/ - FACIT has announced ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" ... commercialization of a portfolio of first-in-class WDR5 inhibitors ... such as WDR5 represent an exciting class of ... precision medicine for cancer patients. Substantial advances have ...
Breaking Biology Technology:
(Date:6/15/2016)... 2016 Transparency Market Research ... Market by Application Market - Global Industry Analysis Size Share ... the report, the  global gesture recognition market  was ... is estimated to grow at a CAGR of ... Increasing application of gesture recognition technology ...
(Date:6/2/2016)... , June 2, 2016 The ... has awarded the 44 million US Dollar project, for ... Embossed Vehicle Plates including Personalization, Enrolment, and IT Infrastructure ... leader in the production and implementation of Identity Management Solutions. ... January, however Decatur was selected for ...
(Date:5/20/2016)... MINNEAPOLIS , May 20, 2016  VoiceIt ... technology partnership with VoicePass. By working ... user experience.  Because VoiceIt and VoicePass take slightly ... two engines increases both security and usability. ... expressed excitement about this new partnership. ...
Breaking Biology News(10 mins):