Novel Potential Treatment For Autoimmune Diseases Inspired By Mother Nature

Main Category: Multiple Sclerosis
Also Included In: Arthritis / Rheumatology;  Immune System / Vaccines
Article Date: 16 Oct 2012 – 3:00 PDT

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Novel Potential Treatment For Autoimmune Diseases Inspired By Mother Nature
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Reproducing a rare type of B cell in the laboratory and infusing it back into the body may provide an effective treatment for severe autoimmune diseases such as multiple sclerosis or rheumatoid arthritis, according to researchers at Duke University Medical Center.
The findings, which were demonstrated in mice, highlight the unique properties of a subset of B cells that normally controls immune responses and limits autoimmunity, in which an organism mistakenly attacks its own healthy tissue. The work appears Oct. 14, 2012, in the journal Nature.
B cells are the component of the immune system that creates antibodies, which fight pathogens like bacteria and viruses. However, a small subset of B cells, called regulatory B cells, works to suppress immune responses. These B cells are characterized by a cell-signaling protein called interleukin-10 (IL-10), giving these regulatory B cells the name B10 cells.
While B10 cells are small in number, they are important for controlling inflammation and autoimmunity. B10 cells can also limit normal immune responses during infections, reducing inadvertent damage to healthy body tissue.
“Regulatory B cells are a fairly new finding that we’re just beginning to understand,” said Thomas F. Tedder, PhD, professor of immunology at Duke and study author. “B10 cells are important because they make sure an immune response doesn’t get carried away, resulting in autoimmunity or pathology. This study shows for the first time that there is a highly controlled process that determines when and where these cells produce IL-10.”
Tedder and his colleagues studied the process of IL-10 production in the B10 cells of mice. Creating IL-10 requires physical interactions between B10 cells and T cells, which play a role in turning on the immune system.
The researchers found that B10 cells only respond to very specific antigens. Recognizing these antigens drives the function of B10 cells, causing them to turn off certain T cells when they bind the same antigen to prevent them from harming healthy tissue.
With this understanding of B10 cells, researchers set out to learn whether B10 cells could be harnessed as a cellular therapy, given their ability to regulate immune responses and autoimmunity.
“Since B10 cells are extremely rare, it was important that we find a feasible solution to reproduce these cells outside the body to make them available,” Tedder said.
The researchers learned that the B10 cells could be isolated from the body and would maintain their ability to regulate immune responses. Moreover, they could be reproduced in large numbers.
“Normal B cells usually die quickly when cultured, but we have learned how to expand their numbers by about 25,000-fold. However, the rare B10 cells in the cultures expand their numbers by four-million-fold, which is remarkable. Now, we can take the B10 cells from one mouse and increase them in culture over nine days to where we can effectively treat 8,000 mice with autoimmune disease,” said Tedder.

When a small amount of B10 cells were introduced into mice with multiple sclerosis-like autoimmune disease, their symptoms were significantly reduced, essentially turning off the disease.

“B10 cells will only shut off what they are programmed to shut off. If you have rheumatoid arthritis, you would want cells that would only go after your rheumatoid arthritis,” continued Tedder. “This research shows that we may have the potential to unharness regulatory cells, make millions of copies, and introduce them back into someone with autoimmune disease to shut down the disease. This may also treat transplanted organ rejection.”

Additional research is needed to learn how to expand human B10 cells and determine how B10 cells behave in humans, building on the study’s insights into the mechanisms behind their function and autoimmunity.

“Autoimmune diseases are very complicated, so creating a single therapy that allows us to go after multiple disease targets without causing immunosuppression has proven to be difficult.” Tedder said. “Here, we’re hoping to take what Mother Nature has already created, improve on it by expanding the cells outside of the body, and then put them back in to let Mother Nature go back to work.”

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our multiple sclerosis section for the latest news on this subject.
In addition to Tedder, Duke study authors include Ayumi Yoshizaki, Tomomitsu Miyagaki, David J. DiLillo, Takashi Matsushita, Mayuka Horikawa, Evgueni I. Kountikov, and Jonathan C. Poe. Rosanne Spolski and Warren J. Leonard contributed to this study from the National Heart, Lung, and Blood Institute, National Institutes of Health.
The research was supported by grants from the National Institutes of Health (AI56363 and AI057157), the Lymphoma Research Foundation, and the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH.Duke University Medical Center
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Hope For New Autoimmune Disease Treatment Using Rare Immune Cells

Main Category: Multiple Sclerosis
Also Included In: Arthritis / Rheumatology;  Immune System / Vaccines
Article Date: 15 Oct 2012 – 15:00 PDT

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Hope For New Autoimmune Disease Treatment Using Rare Immune Cells
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A new study in mice where researchers replicated a rare type of immune cell in the lab and then infused it back into the body, is raising hope for a new treatment for severe autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.
The researchers, from Duke University Medical Center in the US, write about their work on a type of B cell, in a paper that was published online in Nature at the weekend.

B Cells

B cells are immune cells that create antibodies to attack unwanted pathogens like bacteria and viruses.
The type that the researchers on this study focused on are known as regulatory B cells or B10, after interleukin-10 (IL-10), a cell-signalling protein that the cells use.
B10 cells help control immune response and limit autoimmunity, which is where the immune system attacks the body’s own healthy tissue as if it were an unwanted pathogen.
Although there aren’t many of them, B10 cells play a key role in controlling inflammation: they limit normal immune response during inflammation, thus averting damage to healthy tissue.

Regulating Immune Response Is a Highly Controlled Process

Study author Thomas F. Tedder is a professor of immunology at Duke. He says in a statement that we are only just beginning to understand these recently discovered B10 cells.
He says these regulatory B cells are important because they “make sure an immune response doesn’t get carried away, resulting in autoimmunity or pathology”.
“This study shows for the first time that there is a highly controlled process that determines when and where these cells produce IL-10,” he adds.

What they Did

For their study, Tedder and colleagues used mice to study how B10 cells produce IL-10. For IL-10 production to start, the B10 cells have to interact with T cells, which are involved in switching on the immune system.
They found B10 cells only react to certain antigens. They found that binding to these antigens makes the B10 cells turn off some of the T cells (when they come across the same antigen). This stops the immune system from harming healthy tissue.
This was a new insight into the function of B10 cells that spurred the researchers to see if they could take this further: what if it were possible to use this cellular control mechanism to regulate immune responses, particularly in respect of autoimmunity?

Replicating Large Numbers Outside the Body

B10 cells however are not common, they are extremely rare. So Tedder and colleagues had to find a way to make a ready supply of them outside the body.
They found a way to isolate the B10 cells without damaging their ability to control the immune responses. And they found a way to replicate them in large numbers, as Tedder explains:
“Normal B cells usually die quickly when cultured, but we have learned how to expand their numbers by about 25,000-fold.”
“However, the rare B10 cells in the cultures expand their numbers by four-million-fold, which is remarkable. Now, we can take the B10 cells from one mouse and increase them in culture over nine days to where we can effectively treat 8,000 mice with autoimmune disease,” he adds.

Influencing Autoimmunity

The next stage was to try out the new B10 cells: could they influence autoimmunity sufficiently to affect disease symptoms?
They found when they introduced a small number of B10 cells into mice bred to have a disease similar to multiple sclerosis, their symptoms lessened significantly.
“B10 cells will only shut off what they are programmed to shut off,” explains Tedder.

If you have rheumatoid arthritis, you would want cells that would only go after your rheumatoid arthritis,” he adds.

Implications

He and his colleagues suggest their work shows there is potential to remove regulatory cells, replicate them in their millions, and put them back in the body of a person with an autoimmune disease and it will effectively “shut down the disease”, as Tedder describes it:

“This may also treat transplanted organ rejection,” he adds.

The researchers call for more studies to learn how to replicate human B10 cells, and find out how they behave in humans.

Autoimmune diseases are complex, so making a single therapy that targets several diseases without causing immunosuppression is not easy, Tedder explains.

“Here, we’re hoping to take what Mother Nature has already created, improve on it by expanding the cells outside of the body, and then put them back in to let Mother Nature go back to work,” he says.

Grants from the National Institutes of Health, the Lymphoma Research Foundation, and the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH, helped pay for the study.

Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our multiple sclerosis section for the latest news on this subject.
“Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions”; Ayumi Yoshizaki, Tomomitsu Miyagaki, David J. DiLillo, Takashi Matsushita, Mayuka Horikawa, and others; Nature, published online 14 Oct 2012; DOI:10.1038/nature11501; Link to Abstract
Additional source: Duke University Medical Center.
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n.p. (2012, October 15). “Hope For New Autoimmune Disease Treatment Using Rare Immune Cells.” . Retrieved fromhttp://www.medicalnewstoday.com/articles/251507.php.

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Rheumatoid Arthritis And Other Autoimmune Diseases: New Point Of Focus Found For Treatment

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Also Included In: Immune System / Vaccines
Article Date: 11 Oct 2012 – 1:00 PDT

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Scientists affiliated with VIB and UGent have discovered a mechanism used by the protein A20 to combat inflammation. This could be a very important point of focus in the search for a treatment for autoimmune diseases such as Rheumatoid Arthritis, in which the patient suffers from chronic, uncontrolled inflammation.

Rudi Beyaert (VIB – UGent): We hope that our research can eventually contribute to the development of new therapies against Rheumatoid Arthritis and other auto-immune conditions.”

Friday 12 October is “World Arthritis Day”.
A20, a protein involved in Rheumatoid Arthritis (RA) and other autoimmune conditions

RA is a chronic progressive joint condition that starts with an inflammation of the joint membrane and affects the soft tissues around the joints. In Belgium, the number of RA patients is estimated at 100,000. The actual cause is unknown, but there is evidence that the immune system is disrupted, which causes the body to attack its own tissues and creates inflammation in various joints.

Rudi Beyaert and his research team previously identified the molecule A20 as an important point of focus for the development of new medicines against RA and other autoimmune diseases. A20 appears to exert an anti-inflammatory effect in white blood cells.

For the development of new medicines, it is important to fully understand the anti-inflammatory effect of A20. Previous research has demonstrated that A20 interferes with specific “signaling pathways” in our cells that stimulate the activity of a DNA binding molecule (NF-κB). NF-κB plays a key role in many immunological processes and excessive activation of NF-κB can result in a whole range of “inflammatory diseases”, including arthritis. However, it is still largely unknown how A20 interferes with the activity of NF-κB.

Kelly Verhelst and other scientists in the team of Rudi Beyaert have now mapped the specific interaction between A20 and the NF-κB “signaling pathway”. They demonstrated that a small particle (ZF7) at the end of the A20 protein binds to certain small molecules (ubiquitin chains), which are attached to specific NF-κB signaling proteins in the cell. This makes it impossible for these proteins to communicate with other proteins, thereby disrupting the signal that would normally result in inflammation.

This is very interesting from a scientific point of view, because the VIB scientists have identified a new mechanism that brings us one step closer to the possible development of a new medicine. After all, we now know which part of A20 has an anti-inflammatory effect and how exactly this works. Rudi Beyaert: “Now that we know the importance of this small fragment (ZF7) of A20 for the anti-inflammatory effect, we can also use it as a point of focus for the development of medicines against various auto-immune diseases. This is one step closer, but we still have a long way to go.”

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our section for the latest news on this subject.
Relevant scientific publication
The research was published in the leading journal The EMBO Journal (Verhelst et al., A20 inhibits LUBAC-mediated NF-κB activation by binding linear polyubiquitin chains via its zinc finger 7., http://www.ncbi.nlm.nih.gov/pubmed/23032186)

Research team
This research was performed by the research team led by Rudi Beyaert (www.vib.be/rudi-beyaert) in the VIB Department of Molecular Biomedical Research, UGhent.

Funding
This research was jointly funded by: VIB, FWO, IWT, Belspo, and UGhent

VIB (the Flanders Institute for Biotechnology)

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New Point Of Focus Found For The Treatment Of Rheumatoid Arthritis And Other Autoimmune Diseases

Main Category: Arthritis / Rheumatology
Article Date: 10 Oct 2012 – 1:00 PDT

New Point Of Focus Found For The Treatment Of Rheumatoid Arthritis And Other Autoimmune Diseases
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Friday 12 October is “World Arthritis Day”.

Scientists affiliated with VIB and UGent have discovered a mechanism used by the protein A20 to combat inflammation. This could be a very important point of focus in the search for a treatment for autoimmune diseases such as Rheumatoid Arthritis, in which the patient suffers from chronic, uncontrolled inflammation.

Rudi Beyaert (VIB – UGent): We hope that our research can eventually contribute to the development of new therapies against Rheumatoid Arthritis and other auto-immune conditions.”

A20, a protein involved in Rheumatoid Arthritis (RA) and other autoimmune conditions
RA is a chronic progressive joint condition that starts with an inflammation of the joint membrane and affects the soft tissues around the joints. In Belgium, the number of RA patients is estimated at 100,000. The actual cause is unknown, but there is evidence that the immune system is disrupted, which causes the body to attack its own tissues and creates inflammation in various joints.

Rudi Beyaert and his research team previously identified the molecule A20 as an important point of focus for the development of new medicines against RA and other autoimmune diseases. A20 appears to exert an anti-inflammatory effect in white blood cells.

Unraveling the details of an interaction

For the development of new medicines, it is important to fully understand the anti-inflammatory effect of A20. Previous research has demonstrated that A20 interferes with specific “signaling pathways” in our cells that stimulate the activity of a DNA binding molecule (NF-κB). NF-κB plays a key role in many immunological processes and excessive activation of NF-κB can result in a whole range of “inflammatory diseases”, including arthritis. However, it is still largely unknown how A20 interferes with the activity of NF-κB.

Kelly Verhelst and other scientists in the team of Rudi Beyaert have now mapped the specific interaction between A20 and the NF-κB “signaling pathway”. They demonstrated that a small particle (ZF7) at the end of the A20 protein binds to certain small molecules (ubiquitin chains), which are attached to specific NF-κB signaling proteins in the cell. This makes it impossible for these proteins to communicate with other proteins, thereby disrupting the signal that would normally result in inflammation.

Research impact

This is very interesting from a scientific point of view, because the VIB scientists have identified a new mechanism that brings us one step closer to the possible development of a new medicine. After all, we now know which part of A20 has an anti-inflammatory effect and how exactly this works. Rudi Beyaert: “Now that we know the importance of this small fragment (ZF7) of A20 for the anti-inflammatory effect, we can also use it as a point of focus for the development of medicines against various auto-immune diseases. This is one step closer, but we still have a long way to go.”

Article adapted by Medical News Today from original press release. Source: Sources: VIB & UGent
Visit our arthritis / rheumatology section for the latest news on this subject.
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n.p. (2012, October 10). “New Point Of Focus Found For The Treatment Of Rheumatoid Arthritis And Other Autoimmune Diseases.” . Retrieved fromhttp://www.medicalnewstoday.com/releases/251279.php.

‘New Point Of Focus Found For The Treatment Of Rheumatoid Arthritis And Other Autoimmune Diseases’

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Rapid Diagnostic Tests Inspired By Nature

Main Category: Medical Devices / Diagnostics
Also Included In: Sexual Health / STDs;  Allergy;  Immune System / Vaccines
Article Date: 02 Oct 2012 – 0:00 PDT

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Rapid Diagnostic Tests Inspired By Nature

By mimicking nature’s own sensing mechanisms, bioengineers at UC Santa Barbara and University of Rome Tor Vergata have designed inexpensive medical diagnostic tests that take only a few minutes to perform. Their findings may aid efforts to build point-of-care devices for quick medical diagnosis of sexually transmitted diseases (STDs), allergies, autoimmune diseases, and a number of other diseases. The new technology could dramatically impact world health, according to the research team.

The rapid and easy-to-use diagnostic test consists of a nanometer-scale DNA “switch” that can quickly detect antibodies specific to a wide range of diseases. The research is described in an article published this month in the Journal of the American Chemical Society.

The design was created by the research group of Kevin W. Plaxco, a professor in UCSB’s Department of Chemistry and Biochemistry. He noted that, despite the power of current diagnostic tests, a significant limitation is that they still require complex laboratory procedures. “Patients typically must wait for days or even weeks to receive the results of most STD tests,” said Plaxco. “The blood sample has to be transported to the lab, its content analyzed by trained personnel, and the results sent back to the doctor’s office. If we can move testing to the point of care, it eliminates the lag between testing and treatment, which would enhance the effectiveness of medical interventions, and, for infectious diseases like STDs, reduce transmission.”

The key breakthrough underlying this new technology came from observing nature. “All creatures, from bacteria to humans, monitor their environments using amazing ‘molecular nanoswitches’ that signal the presence of a specific target by changing their structure,” said Alexis Vallée-Bélisle, a postdoctoral scholar and co-first author of the study. “For example, on the surface of our cells, there are millions of receptor proteins that detect various molecules by switching from an ‘off state’ to an ‘on state.’ The beauty of these switches is that they are able to work directly in very complex environments such as whole blood.”

Plaxco’s research group teamed with Francesco Ricci, professor at University of Rome Tor Vergata and co-first author of the paper, to build synthetic molecular switches that signal their state via a change in electric current. This change in current can be measured using inexpensive electronics similar to those in the home glucose test meter used by diabetics to check their blood sugar. Using these “nature-inspired” nanoswitches, the researchers were able to detect anti-HIV antibodies directly in whole blood in less than five minutes.

“A great advantage of these electrochemical nanoswitches is that their sensing principle can be generalized to many different targets, allowing us to build inexpensive devices that could detect dozens of disease markers in less than five minutes in the doctor’s office or even at home,” said Ricci.

The authors noted that it may take several years to bring the devices to the market.

The additional co-authors are Fan Xia of Huazhong University of Science and Technology in Wuhan, China; and Takanori Uzawa of Hokkaido University in Sapporo, Japan.
This work was funded by the National Institute of Health, the Fond Québécois de la Recherche sur la Nature et les Technologies; the Italian Ministry of University and Research (MIUR) project “Futuro in Ricerca;” and the Bill & Melinda Gates Foundation, through the Grand Challenges Explorations Grant.
University of California – Santa Barbara
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Are We Too Clean? Letting Kids Get Dirty and Germy

It’s the basic nature of young children to touch the very things in their environment that their parents find most disgusting. Just try to keep your 1-year-old from sticking the dog’s bone in her mouth!

Epidemic-scale flu seasons have health authorities imploring regular hand washing, and with talk of sanitizer gel like it was liquid gold, it’s tough not to worry about what your children are getting into and the ultimate impact it will have on their health.

Infectious diseases are a legitimate cause for concern, but some would argue that our society has gone overboard when it comes to protecting our kids from germs.

How clean an environment do our kids really need for good health? Here’s what experts told WebMD.

Hygiene Hypothesis

A mounting body of research suggests that exposing infants to germs may offer them greater protection from illnesses such as allergies and asthma later on in life.

This line of thinking, called the “hygiene hypothesis,” holds that when exposure to parasites, bacteria, and viruses is limited early in life, children face a greater chance of having allergies, asthma, and other autoimmune diseases during adulthood.

In fact, kids with older siblings, who grew up on a farm, or who attended day care early in life seem to show lower rates of allergies. 

Just as a baby’s brain needs stimulation, input, and interaction to develop normally, the young immune system is strengthened by exposure to everyday germs so that it can learn, adapt, and regulate itself, notes Thom McDade, PhD, associate professor and director of the Laboratory for Human Biology Research at Northwestern University.

Exactly which germs seem to do the trick hasn’t yet been confirmed. But new research offers clues.

In a recent study, McDade’s team found that children who were exposed to more animal feces and had more cases of diarrhea before age 2 had less incidence of inflammation in the body as they grew into adulthood.

Inflammation has been linked to many chronic adulthood illnesses, such as heart disease, diabetes, and Alzheimer’s.

“We’re moving beyond this idea that the immune system is just involved in allergies, autoimmune diseases, and asthma to think about its role in inflammation and other degenerative diseases,” McDade says. “Microbial exposures early in life may be important… to keep inflammation in check in adulthood.”

Purging Germs: Health Booster or Bad Idea?

Most of the germs lurking about our environment and that live on our bodies are not only harmless; they’ve been with us for millennia, says Martin Blaser, MD, professor of internal medicine at New York University. 

As human behavior has changed over the past half century, many microbes, such as some that live in the gut, are disappearing.

“These perform important physiological functions but because of modern life they are changing and some are disappearing,” Blaser says. “Those disappearances have consequences — some good, some bad.”

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