Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genetic Cause Discovered for Systemic Lupus Erythematosus

20.09.2007
Mutations in a gene researchers call TREX1 is one cause for systemic lupus erythematosus (SLE), a severe and incurable autoimmune disease. This is the result of a new study headed by Professor Norbert Hübner from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Dr. Min Ae Lee-Kirsch from the Technical University Dresden, (both in Germany) in collaboration with scientists from Finland, Sweden, the United Kingdom, and the USA. The study has now been published in the latest issue of Nature Genetics (Vol. 39, No. 9, pp. 1065-1067, 2007).

The exact causes for SLE are still unknown. Triggers are thought to include viruses, the sunlight, drug reactions, or a specific genetic predisposition. Symptoms of SLE can be inflammations of the skin, the joints, the heart, the lungs, the kidney, and the nervous system. The name of the disease refers to red spots on the skin which resemble the bites of a wolfe (latin: lupus). As the disease can affect any part of the body, it is "systemic". SLE belongs to the group of autoimmune diseases, because the body's immune system attacks its own healthy cells and tissues, causing inflammations. About 40,000 individuals are affected in Germany, most of them are women.

In a family suffering from a rare form of lupus, Dr. Lee-Kirsch and Professor Hübner discovered various mutations in the gene TREX1. Hence, they wanted to know if mutations in TREX1 also play a role in SLE, the most common form of lupus. Collecting blood samples from patients with SLE from the UK, Germany, and Finland, the researcher compared them with samples from healthy individuals. As suspected, patients with SLE carried mutations in the TREX1 gene whereas healthy individuals did not. Nevertheless, the mutations found in TREX1 are not responsible for all types of SLE.

The product of the gene TREX1 is a protein which plays a role in apoptosis, a program in which cells literally induce their own death when defective. Thus, apoptosis protects the body from harm. Once apoptosis starts, TREX1 gets rid of its junctions in the cytoplasm and translocates into the nucleus of a damaged cell to digest its DNA.

... more about:
»Genetic »Lupus »SLE »TREX1 »apoptosis »mutations

Mutations in TREX1, however, change part of the protein with which it is chained to the cell's cytoplasm. In the case of apoptosis, TREX1 gets rid of its molecular chains, translocates into the cell's nucleus, and spreads to other parts of the cell too. The immune system seems to be mislead as it produces autoantibodies against these cell particles and also against other healthy cells. Why autoantibodies are produced still remains unclear. "Further studies will have to shed light onto this problem", stresses Professor Hübner.

*Mutations in the 3´-5´ DNA exonuclease TREX1 are associated with systemic lupus erythematosus

Min Ae Lee-Kirsch1, Maolian Gong2#, Dipanjan Chowdhury3#, Lydia Senenko1#, Kerstin Engel1#, Young-Ae Lee2,4#, Udesh de Silva5, Suzanna L. Bailey5, Torsten Witte6, Timothy J. Vyse7, Juha Kere8, Christiane Pfeiffer9, Scott Harvey10, Andrew Wong7, Sari Koskenmies11,12, Oliver Hummel2, Klaus Rohde2, Reinhold E. Schmidt6, Anna F. Dominiczak13, Manfred Gahr1, Thomas Hollis5, Fred W. Perrino10, Judy Lieberman3, & Norbert Hübner2

1Klinik für Kinder- und Jugendmedizin, Technische Universität Dresden, 01307 Dresden, Germany
2Max-Delbrück-Center for Molecular Medicine (MDC), Berlin-Buch, Germany
3CBR Institute for Biomedical Research, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 01225, USA
4Charité - Universitätsmedizin Berlin, Pediatric Pneumology and Immunology, Campus Virchow-Klinikum, 13553 Berlin, Germany
5Center for Structural Biology, Department of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA
6Medizinische Hochschule Hannover, Klinische Immunologie, 30625 Hannover, Germany
7Imperial College, Faculty of Medicine, Section of Rheumatology and Molecular Genetics, Hammersmith Hospital, London W12 0NN, UK.
8Karolinska Institute, Department of Biosciences and Nutrition, and Clinical Research Centre, 14157 Huddinge, Sweden
9Klinik für Dermatologie, Technische Universität Dresden, 01307 Dresden, Germany
10Department of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA
11University of Helsinki, Department of Medical Genetics and 12Department of Dermatology, 00014 Helsinki, Finland
13Department of Medicine and Therapeutics, Western Infirmary, Glasgow University, Glasgow G11 6NT, UK

#These authors contributed equally.

Correspondence requests should be addressed to M. L.-K. (minae.lee-kirsch@uniklinikum-dresden.de) and N. H. (nhuebner@mdc-berlin.de)

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
Weitere Informationen:
http://www.nature.com/ng/journal/v39/n9/pdf/ng2091.pdf
http://www.nature.com/ng/journal/v39/n9/suppinfo/ng2091_S1.html
http://www.mdc-berlin.de/englisch/research/research_areas/cardiovascular/huebner.htm

http://en.wikipedia.org/wiki/Lupus_erythematosus

Barbara Bachtler | idw
Further information:
http://www.mdc-berlin.de/englisch/about_the_mdc/public_relations/e_index.htm

Further reports about: Genetic Lupus SLE TREX1 apoptosis mutations

More articles from Life Sciences:

nachricht Life on the edge prepares plants for climate change
18.12.2017 | Max-Planck-Institut für Entwicklungsbiologie

nachricht Lipid nanodiscs stabilize misfolding protein intermediates red-handed
18.12.2017 | Technische Universität München

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Error-free into the Quantum Computer Age

A study carried out by an international team of researchers and published in the journal Physical Review X shows that ion-trap technologies available today are suitable for building large-scale quantum computers. The scientists introduce trapped-ion quantum error correction protocols that detect and correct processing errors.

In order to reach their full potential, today’s quantum computer prototypes have to meet specific criteria: First, they have to be made bigger, which means...

Im Focus: Search for planets with Carmenes successful

German and Spanish researchers plan, build and use modern spectrograph

Since 2016, German and Spanish researchers, among them scientists from the University of Göttingen, have been hunting for exoplanets with the “Carmenes”...

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Single-photon detector can count to 4

18.12.2017 | Information Technology

Quantum memory with record-breaking capacity based on laser-cooled atoms

18.12.2017 | Physics and Astronomy

How much soil goes down the drain -- New data on soil lost due to water

18.12.2017 | Agricultural and Forestry Science

VideoLinks
B2B-VideoLinks
More VideoLinks >>>