Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Insights into the Disease Mechanism of Vasculitis. Potential Target for Specific Therapy

16.05.2007
A potential therapeutic target for autoimmune vasculitis has been identified by researchers of the Franz Volhard Clinic for Cardiovascular Diseases (FVK) of the Charité – University Medicine Berlin/HELIOS-Klinikum and the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch.

They discovered that a specific surface receptor (NB1) mediates the expression of a molecule (autoantigen) on the surface of certain white blood cells, where the immune system recognizes and binds it. This reaction starts the inflammation process. Thus, NB1 is a potential drug target for ANCA-associated vasculitis, as Dr. Sibylle von Vietinghoff (FVK), Professor Friedrich Luft (FVK, MDC) and Professor Ralph Kettritz (FVK) report in the American journal Blood (Vol. 109, No. 10, pp. 4487-4493, May 15, 2007)*.

Autoimmune vasculitis is a broad term encompassing a group of disorders characterized by blood vessel inflammation. It is triggered by antibodies formed by the immune system which are no longer able to distinguish between “self” and “non-self”. The antibodies target the most common white blood cells, the neutrophil granulocytes, or more precisely an enzyme that is normally found in the cell plasma of these blood cells, proteinase 3 (PR3).

Neutrophil granulocytes are part of the immune system, and their primary function is to attack viruses and bacteria. In the cell plasma of all neutrophil granulocytes, the enzyme proteinase 3 (PR3) is present. PR3 plays a role in one form of vasculitis because it elicits the formation of autoantibodies. These antibodies are therefore called ANCA (antineutrophil cytoplasmatic autoantibodies).

However, ANCA autoantibodies only attack the white blood cells which “display” the enzyme PR3 on their surface. The blood cells which retain the enzyme inside the cell away from the cell surface avoid the attack of the autoantibodies. The binding of the ANCA antibodies to the PR3 localized on the cell membrane activates the white blood cells, which thereupon attack the body’s own structures and trigger the inflammation processes in the blood vessels. The resulting inflammation can affect any and all organs and become life-threatening.

Receptor protein

Prior to this study it was not known how the enzyme is presented on the membrane surface of the blood cells. Dr. von Vietinghoff and her colleagues in Berlin-Buch were able to show that it has a “helper” presenting it on the surface of the blood cells: the membrane anchor protein NB1 (CD177). For their study they tested and compared blood samples obtained from 200 healthy volunteer donors and patients with ANCA vasculitis. The researchers discovered that the enzyme PR3 and the receptor NB1 were more often found on the surfaces of blood cells in patients with ANCA vasculitis. Using molecular techniques the researchers were able to prove that NB1 is necessary for PR3 membrane presentation.

Aim – Development of a specific therapy

NB1 therefore appears to be a promising therapeutic target, according to Sibylle von Vietinghoff, Ralph Kettritz and Friedrich Luft. Although today there are treatments for vasculitis and related disorders such as Wegener’s granulomatosis, a rare but serious disease which affects all body organs including the kidneys, currently used drugs suppress the entire immune system. The disadvantage is that this makes patients more vulnerable to infection.

With unspecific immune therapy and dialysis, the kidneys of the affected patients often recover their function. “It is one of the few kidney diseases in which patients are able to come off dialysis,” Ralph Kettritz said. But a risk of recurrence always remains. If NB1 could be inhibited and PR3 expression on the blood cell surfaces prevented, vasculitis could be better controlled or even cured and recurrences avoided. “That is why our findings provide hope for patients with vasculitis,” he said. “A specific therapy approach based on our study may hold the key to overcoming the disease.”

Barbara Bachtler | alfa
Further information:
http://bloodjournal.hematologylibrary.org/

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>