Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecule linked to autoimmune disease relapses identified at Stanford

05.12.2006
The ebb and flow of such autoimmune diseases as multiple sclerosis, lupus and rheumatoid arthritis has long been a perplexing mystery. But new findings from the Stanford University School of Medicine bring scientists closer to solving the puzzle, identifying a molecule that appears to play a central role in relapses.

The study, to be published in the Dec. 3 advance online edition of Nature Immunology, lays the groundwork for a way to determine when a relapse is about to occur, and could eventually lead to a treatment to prevent relapses. "Right now, there is no good blood test to evaluate when a person is going to have a flare-up," said senior author Larry Steinman, MD, professor of neurology and neurological sciences. "If we had one, we might be able to give them prophylactic preventive medication."

The current study had its genesis five years ago: In a paper published in 2001 in the journal Science, Steinman found that a protein called osteopontin was abundant in multiple sclerosis-affected brain tissue, but not in normal tissue. Since then, other groups have confirmed that osteopontin is elevated just prior to and during a relapse of the disease in M.S. patients.

Although the protein had been known to play a role in bone growth, it was unclear why it would be associated with multiple sclerosis, which results when the immune system attacks the protective myelin sheath surrounding nerve cells.

To explore this question, Eun Mi Hur, PhD, who was then a graduate student in Steinman's lab, began using a mouse model of multiple sclerosis (experimental autoimmune encephalomyletis, or EAE) to investigate how osteopontin could cause these flare-ups. She and Steinman gave osteopontin to mice that had already experienced paralysis, similar to that of an M.S. patient, and found that the mice then experienced a relapse of the disease.

The researchers also found that the relapse would occur sometimes in an area of the brain other than the site of the original attack. For example, after receiving the osteopontin, some animals that had previously suffered paralysis became blind from a condition called optic neuritis. One feature of multiple sclerosis is that the flare-ups can affect different parts of the nervous system at different times.

"When I saw that all mice with EAE relapsed and died from the disease after about a month of osteopontin administration, I was surprised," said Hur, the study's first author who is now a postdoctoral scholar at Caltech. "I got a strong belief that a high level of osteopontin in patients' blood and tissue is a major contributor of the relapse and progression of the disease."

Through the mouse studies and molecular characterizations, Hur and Steinman showed that osteopontin - produced by immune cells and brain cells themselves - promotes the survival of the T cells that carry out the damaging attack on myelin; by increasing the number of these T cells, osteopontin increases their destructive potential. These results could be applicable to many other autoimmune diseases, including rheumatoid arthritis, type-1 diabetes and lupus.

Indeed, the effect of osteopontin may severely alter the way the immune system works. Normally, after the immune system does its job - eradicating a microbe, for instance - the response is then dialed down. If this didn't happen, the immune response would go on indefinitely. Imagine a cold or an attack of poison oak that would last forever.

One of the ways that the immune response is muffled is that the activated T cells die in a process known as apoptosis. That is precisely what osteopontin seems to prevent. Osteopontin lets the T cells linger in the blood, ready to attack again. "We don't know exactly what triggers that new attack but the cells certainly are around and ready to do it," said Steinman. So scientists now face the challenge of figuring out how and why osteopontin is produced. "We're back to the chicken-and-the-egg problem," said Steinman. "We know the egg, so why did the chicken lay it" That is a trickier problem to work out."

Even without knowing the answer to that question, there is one inviting practical use of their observations: Osteopontin could be used as a marker of an impending relapse. What's more, if the protein could be blocked, it might thwart the relapse from ever occurring. Steinman's lab is working to develop antibodies to inactivate the protein's effect. "It's still a long road between saying we want to do it and getting the antibodies, getting it approved by the FDA and getting it tested," said Steinman, "but we are determined to do that."

Still, Steinman offered a caveat. Researchers may find that blocking osteopontin has undesirable side effects. The protein may serve other purposes in addition to promoting survival of immune cells. It could also be vital to the body's ability to produce myelin, a function that could cause severe problems if disrupted. "Like a lot of important biological molecules, osteopontin has a Janus-like quality - a bad side and a good side," Steinman said. "We're going to be extremely lucky if we give the antibody opposing osteopontin and derive just the good side: We stop the autoimmune attack but don't interfere with the survival of other cells."

Further study will determine whether thwarting osteopontin's effect yields new types of treatments for autoimmune diseases, but regardless, it is likely to lead to discoveries in a host of areas. "I think osteopontin will turn out to be important in a lot of processes, spanning autoimmunity to stem cells," said Steinman. "It's probably going to turn out to be a very basic growth factor."

Mitzi Baker | EurekAlert!
Further information:
http://www.stanford.edu

Further reports about: Osteopontin Steinman T cells autoimmune flare-up multiple sclerosis relapse

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>