Posts tagged immune system
Articles and news from the latest research reports.
Study Suggests Targeting B Cells May Help with MS
A new study suggests that targeting B cells, which are a type of white blood cell in the immune system, may be associated with reduced disease activity for people with multiple sclerosis (MS). The study is released today and will be presented at the American Academy of Neurology’s 66th Annual Meeting in Philadelphia, April 26 to May 3, 2014.
For the study, 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of the drug ofatumumab, which is an anti-B cell antibody, for 24 weeks, with the first 12 weeks making up the placebo-controlled period. The main objective was to determine the effects of ofatumumab dosing regimens compared to placebo on the total number of new brain lesions assessed every four weeks over a 12-week period.
All dose groups including placebo showed lesion activity in the first four weeks with lesion suppression in all ofatumumab dose groups from weeks four to12. Researchers measured the amount of B cells in participants and compared that to the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.
The researchers found that when B cells were reduced to below a threshold of 64 cells per microliter, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells per microliter, compared with 16 lesions without treatment.
The most common side effects, defined as those occurring in at least five percent of participants and at a rate twice that of placebo for weeks zero to12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection and nerve pain.
Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, and a member of the American Academy of Neurology, said the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.
“These results need to be validated, of course, but the findings are interesting,” Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.” Ofatumumab is not approved anywhere in the world for use in the treatment of multiple sclerosis.
Researchers find link between sleep and immune function in fruit flies
When we get sick it feels natural to try to hasten our recovery by getting some extra shuteye. Researchers from the Perelman School of Medicine at the University of Pennsylvania found that this response has a definite purpose, in fruitflies: enhancing immune system response and recovery to infection. Their findings appear online in two related papers in the journal Sleep, in advance of print editions in May and June.
"It’s an intuitive response to want to sleep when you get sick," notes Center for Sleep and Circadian Neurobiology research associate Julie A. Williams, PhD. "Many studies have used sleep deprivation as a means to understand how sleep contributes to recovery, if it does at all, but there is surprisingly little experimental evidence that supports the notion that more sleep helps us to recover. We used a fruitfly model to answer these questions." Along with post-doctoral fellow, Tzu-Hsing Kuo, PhD, Williams conducted two related studies to directly examine the effects of sleep on recovery from and survival after an infection.
In the first paper, they took a conventional approach by subjecting fruit flies to sleep deprivation before infecting them with either Serratia marcescens or Pseudomonas aeruginosa bacteria. Both the sleep-deprived flies and a non-sleep-deprived control group displayed increased sleep after infection, what the experimenters call an “acute sleep response.”
Unexpectedly, the pre-infection, sleep-deprived flies had a better survival rate. “To our surprise they actually survived longer after the infection than the ones who were not sleep-deprived,” notes Williams. The Penn team found that prior sleep deprivation made the flies sleep for a longer period after infection as compared to the undisturbed controls. They slept longer and they lived longer during the infection. Inducing sleep deprivation after infection rather than before made little difference, as long as the infected flies then got adequate recovery sleep. “We deprived flies of sleep after infection with the idea that if we blocked this sleep, things would get worse in terms of survival,” Williams explains. “Instead they got better, but not until after they had experienced more sleep.”
Sleep deprivation increases activity of an NFkB transcription factor, Relish, which is also needed for fighting infection. Flies without the Relish gene do not experience an acute sleep response and very quickly succumb to infection. But, when these mutants are sleep-deprived before infection, they displayed increased sleep and survival rates after infection. The team then evaluated mutant flies that lacked two varieties of NFkB (Relish and Dif). When flies lacked both types of NFkB genes, sleep deprivation had no effect on the acute sleep response, and the effect on survival was abolished. Flies from both sleep-deprived and undisturbed groups succumbed to infection at equal rates within hours.
"Taken together, all of these data support the idea that post-infection sleep helps to improve survival," Williams says.
In the second study, the researchers manipulated sleep through a genetic approach. They used the drug RU486 to induce expression of ion channels to alter neuronal activity in the mushroom body of the fly brain, and thereby regulate sleep patterns. Compared to a control group, flies that were induced to sleep more, and for longer periods of time for up to two days before infection, showed substantially greater survival rates. The flies with more sleep also showed faster and more efficient rates of clearing the bacteria from their bodies. “Again, increased sleep somehow helps to facilitate the immune response by increasing resistance to infection and survival after infection,” notes Williams.
Because the genetic factors investigated by the Penn team, such as the NFkB pathway, are preserved in mammals, the relative simplicity of the Drosophila model provides an ideal avenue to explore basic functions like sleep. “Investigators have been working on questions about sleep and immunity for more than 40 years, but by narrowing down the questions in the fly we’re now in a good position to identify potentially novel genes and mechanisms that may be involved in this process that are difficult to see in higher animals,” explains Williams.
"These studies provide new evidence of the direct and functional effects of sleep on immune response and of the underlying mechanisms at work. The take-home message from these papers is that when you get sick, you should sleep as much as you can — we now have the data that supports this idea," she concludes.
Is Parkinson’s an Autoimmune Disease?
The cause of neuronal death in Parkinson’s disease is still unknown, but a new study proposes that neurons may be mistaken for foreign invaders and killed by the person’s own immune system, similar to the way autoimmune diseases like type I diabetes, celiac disease, and multiple sclerosis attack the body’s cells. The study was published April 16, 2014, in Nature Communications.
(Image caption: Four images of a neuron from a human brain show that neurons produce a protein (in red) that can direct an immune attack against the neuron (green). Credit: Carolina Cebrian.)
“This is a new, and likely controversial, idea in Parkinson’s disease; but if true, it could lead to new ways to prevent neuronal death in Parkinson’s that resemble treatments for autoimmune diseases,” said the study’s senior author, David Sulzer, PhD, professor of neurobiology in the departments of psychiatry, neurology, and pharmacology at Columbia University College of Physicians & Surgeons.
The new hypothesis about Parkinson’s emerges from other findings in the study that overturn a deep-seated assumption about neurons and the immune system.
For decades, neurobiologists have thought that neurons are protected from attacks from the immune system, in part, because they do not display antigens on their cell surfaces. Most cells, if infected by virus or bacteria, will display bits of the microbe (antigens) on their outer surface. When the immune system recognizes the foreign antigens, T cells attack and kill the cells. Because scientists thought that neurons did not display antigens, they also thought that the neurons were exempt from T-cell attacks.
“That idea made sense because, except in rare circumstances, our brains cannot make new neurons to replenish ones killed by the immune system,” Dr. Sulzer says. “But, unexpectedly, we found that some types of neurons can display antigens.”
Cells display antigens with special proteins called MHCs. Using postmortem brain tissue donated to the Columbia Brain Bank by healthy donors, Dr. Sulzer and his postdoc Carolina Cebrián, PhD, first noticed—to their surprise—that MHC-1 proteins were present in two types of neurons. These two types of neurons—one of which is dopamine neurons in a brain region called the substantia nigra—degenerate during Parkinson’s disease.
To see if living neurons use MHC-1 to display antigens (and not for some other purpose), Drs. Sulzer and Cebrián conducted in vitro experiments with mouse neurons and human neurons created from embryonic stem cells. The studies showed that under certain circumstances—including conditions known to occur in Parkinson’s—the neurons use MHC-1 to display antigens. Among the different types of neurons tested, the two types affected in Parkinson’s were far more responsive than other neurons to signals that triggered antigen display.
The researchers then confirmed that T cells recognized and attacked neurons displaying specific antigens.
The results raise the possibility that Parkinson’s is partly an autoimmune disease, Dr. Sulzer says, but more research is needed to confirm the idea.
“Right now, we’ve showed that certain neurons display antigens and that T cells can recognize these antigens and kill neurons,” Dr. Sulzer says, “but we still need to determine whether this is actually happening in people. We need to show that there are certain T cells in Parkinson’s patients that can attack their neurons.”
If the immune system does kill neurons in Parkinson’s disease, Dr. Sulzer cautions that it is not the only thing going awry in the disease. “This idea may explain the final step,” he says. “We don’t know if preventing the death of neurons at this point will leave people with sick cells and no change in their symptoms, or not.”
(Source: newsroom.cumc.columbia.edu)
Scientists discover a protein in nerves that determines which brain connections stay and which go
A newborn baby, for all its cooing cuddliness, is a data acquisition machine, absorbing information to finish honing the job of brain wiring that started before birth. This is true nowhere more so than the eyes, which start life peering at a blurry world and within months can make out a crisp, three-dimensional image of a mobile dangling overhead.
This process of refining the brain’s wiring involves cutting off some of the excess nerve connections we have at birth while strengthening connections we use all the time. Some estimates show that as many as half of the brain’s connections formed during development are clipped back as the final wiring takes shape.
Carla Shatz, the David Starr Jordan Director of Stanford Bio-X, and her team, including postdoctoral researcher Hanmi Lee and Bio-X Graduate Fellow Jaimie Adelson, recently found a protein that is essential for the brain to remove those excess connections. The team specifically showed a role for the protein in the developing visual system in mice, but the work appears to apply broadly across the developing brain. They published their findings online March 30 in the journal Nature.
Shatz said the discovery helps clear up something that has been a mystery to those who study brain development: How does the decision get made to eliminate some connections? It also settles a decade-long debate over whether the nervous system or the immune system is making those decisions. (Spoiler alert: It’s the nervous system.)
A single vision
"Vision is a challenging problem because you have two eyes and only one view of the world," said Shatz, who is the Sapp Family Provostial Professor and professor of biology and of neurobiology. "There’s a very beautiful set of wiring steps that makes sure the eyes are pointed at the same place and the two images get aligned."
Shatz said the rule of which connections the brain cuts back to create that single vision follows a simple mantra: “Fire together, wire together. Out of sync, lose your link.” Or rather, if early in life the left sides of both eyes see the same duck motif wallpaper, those neurons fire together and stay linked up. When the top of one eye and bottom of the other eye form a connection, the nerves fire out of sync, and the connection weakens and is eventually pruned back. Over time, the only connections that remain are between parts of the two eyes that are seeing the same thing.
The ability to detect which nerves fire out of sync and should therefore lose their link requires the protein Shatz’s team reported, which goes by the name of MHC Class I D, or D for short. This protein is one that is famous for its role in the immune system, but only in the past decade has Shatz’s team started building a case for D’s independent role in the brain.
Two camps, one protein
In 2000 Shatz first published work suggesting that a group of immune proteins called MHC in mice and HLA in people played a role in the developing nervous system. At the time, this caused a stir among immunologists, who were surprised to find their proteins showing up in the brain.
Lawrence Steinman, professor of neurology and neurological sciences and of pediatrics at Stanford School of Medicine, has followed Shatz’s work from the perspective of both a neurologist and immunologist. “One of the reasons that I think the research is so interesting is that it shows us that molecules thought to be the province of one group can be in another,” he said, adding, “It slowed the prevailing idea that people believed that some molecules were the domain of one camp.”
Shatz is in the privileged position of directing Stanford Bio-X, which includes faculty members and students from both immunology and the neurological sciences. She said being able to talk about her work and collaborate with this mix of colleagues has helped break down barriers in thinking about her unexpected findings.
After the initial discovery, Shatz went on to show that two of those MHC proteins – D and its sister protein K – seemed to be important in eliminating connections in the brain. Mice genetically engineered to lack both K and D had poorly functioning immune systems and also ended up with the visual system in a jumble, with unrelated parts of the two eyes forming connections. Without D and K the mice weren’t detecting which connections fired out of sync, so those connections didn’t lose their link.
After Shatz published that work, some immunologists argued that perhaps D and K were necessary for brain remodeling only because of their key function in the immune system. “They were saying that the immune system was telling the nervous system what to prune,” Shatz said.
It was a theory, but not one Shatz agreed with. Her feeling was that just because D and K were first found in the immune system didn’t mean they couldn’t have a unique role in the brain. “The nervous system has just as much right to these immune proteins as the immune system,” Shatz said. Her most recent work makes that point clear.
D on the brain
Shatz and her group worked with the mice that were lacking D and K everywhere, then used genetic engineering tricks to add D back, but only in the neurons. These mice still had poorly functioning immune systems, but had perfectly normal eye connections. In these mice, the nerves were able to determine which connections to cut and which to keep, even without the immune system.
Steinman said the work settles the issue of whether D is acting in the brain separate from its role in the immune system. “If Carla had studied MHC proteins before the immunologists, then we would consider them to be part of the nervous system. They clearly have major roles in both the nervous system and the immune system,” he said.
The group went on to show that the presence of D alters the composition of other proteins on the nerve cell surface that are in charge of receiving signals from other nerves. Her team thinks that it is this difference in how the nerve receives signals with or without D that makes the pruning process go awry.
Essentially, without D all nerve connections appear to be firing together and therefore they stay wired together.
Shatz says that in addition to explaining an important part of brain development, the work could also provide a new avenue for studying schizophrenia. Some studies have shown that people with mutations in the human genes related to D (called HLA genes) are more prone to the disease. Other studies have associated schizophrenia with improperly formed connections in the brain. Shatz suggests that this new role for D in the brain could mean that the pruning process has gone awry in schizophrenia. The group plans to explore this idea further, as well as to tease apart what D is doing to alter the composition of neurotransmitter receptors on the nerve cell surface.
Immune System Has Dramatic Impact on Children’s Brain Development
New research from the University of Virginia School of Medicine has revealed the dramatic effect the immune system has on the brain development of young children. The findings suggest new and better ways to prevent developmental impairment in children in developing countries, helping to free them from a cycle of poverty and disease, and to attain their full potential.
U.Va. researchers working in Bangladesh determined that the more days infants suffered fever, the worse they performed on developmental tests at 12 and 24 months. They also found that elevated levels of inflammation-causing proteins in the blood were associated with worse performance, while higher levels of inflammation-fighting proteins were associated with improved performance.
“The problem we sought to address was why millions of young children in low- and middle-income countries are not attaining their full developmental potential,” said lead author Nona Jiang, who performed the research while an undergraduate student in the laboratory of Dr. William Petri Jr. “Early childhood is an absolutely critical time of brain development, and it’s also a time when these children are suffering from recurrent infections. Therefore, we asked whether these infections are contributing to the impaired development we observe in children growing up in adversity.”
Their findings offer a potential explanation for the developmental impairment seen in children living in poverty. They also offer important direction for doctors attempting to combat the problem: By preventing inflammation, physicians may be able to enhance children’s mental ability for a lifetime.
“We are interested in examining factors that predict healthy child development around the world,” said researcher Dr. Rebecca Scharf of U.Va.’s Department of Pediatrics. “By studying which early childhood influences are associated with hindrances to growth and learning, we will know better where to target interventions for the critical period of early childhood.”
In addition, the finding illuminates the complex relationship between the immune system and cognitive development, an increasingly important area of research that U.Va. has helped pioneer.
“This is a very interesting study, showing, probably for the first time, the link between peripheral cytokine levels and improved cognitive development in humans,” said Jonathan Kipnis, a professor of neuroscience and director of U.Va.’s Center for Brain Immunology & Glia. “What is of the most interest and of a great novelty is the fact that [inflammation-fighting cytokines] have positive correlation with cognitive function. My lab published results showing that these IL-4 cytokines are required for proper brain function in mice, and this work from Dr. Petri’s lab completely independently shows similar correlation in humans.
“I hope the scientific community will appreciate how dramatic the effects of the immune system are on the central nervous system and will invest more efforts in studying and better understanding these complex and intriguing interactions between the body’s two major systems.”
(Source: news.virginia.edu)
Study in Mice Raises Question: Could PTSD Involve Immune Cell Response to Stress?
Chronic stress that produces inflammation and anxiety in mice appears to prime their immune systems for a prolonged fight, causing the animals to have an excessive reaction to a single acute stressor weeks later, new research suggests.
After the mice recovered from the effects of chronic stress, a single stressful event 24 days later quickly returned them to a chronically stressed state in biological and behavioral terms. Mice that had not experienced the chronic stress were unaffected by the single acute stressor.
The study further showed that immune cells called to action as a result of chronic stress ended up on standby in the animals’ spleens and were launched from that organ to respond to the later stressor.
Mice without spleens did not experience the same reactivation with the second stressor, signifying the spleen’s role as a reservoir for primed immune cells to remain until they’re activated in response to another stressor.
The excessive immune response and anxiety initiated by a brief stressor mimic symptoms of post-traumatic stress disorder.
The Ohio State University scientists are cautious about extending their findings to humans. But they say their decade of work with this model of stress suggests that the immune system has a significant role in affecting behavior. And they are the first to study this re-establishment of anxiety in animals with a later acute stressor.
“No one else has done a study of this length to see what happens to recovered animals if we subject them again to stress,” said Jonathan Godbout, a lead author of the study and associate professor of neuroscience at Ohio State. “That retriggering is a component of post-traumatic stress. The previously stressed mice are living a normal rodent life, and then this acute stress brings everything back. Animals that have never been exposed to stress before were unaffected by that one event – it didn’t change behavioral or physiological properties.”
The research is published online in the journal Biological Psychiatry.
(Source: researchnews.osu.edu)
Narcolepsy confirmed as autoimmune disease
Results also partly explain why the 2009 swine flu virus, and a vaccine against it, led to spikes in the sleep disorder.
As the H1N1 swine flu pandemic swept the world in 2009, China saw a spike in cases of narcolepsy — a mysterious disorder that involves sudden, uncontrollable sleepiness. Meanwhile, in Europe, around 1 in 15,000 children who were given Pandemrix — a now-defunct flu vaccine that contained fragments of the pandemic virus — also developed narcolepsy, a chronic disease.
Immunologist Elizabeth Mellins and narcolepsy researcher Emmanuel Mignot at Stanford University School of Medicine in California and their collaborators have now partly solved the mystery behind these events, while also confirming a longstanding hypothesis that narcolepsy is an autoimmune disease, in which the immune system attacks healthy cells.
Narcolepsy is mostly caused by the gradual loss of neurons that produce hypocretin, a hormone that keeps us awake. Many scientists had suspected that the immune system was responsible, but the Stanford team has found the first direct evidence: a special group of CD4+ T cells (a type of immune cell) that targets hypocretin and is found only in people with narcolepsy.
“Up till now, the idea that narcolepsy was an autoimmune disorder was a very compelling hypothesis, but this is the first direct evidence of autoimmunity,” says Mellins. “I think these cells are a smoking gun.” The study is published today in Science Translational Medicine.
Thomas Scammell, a neurologist at Harvard Medical School in Boston, Massachusetts, says that the results are welcome after “years of modest disappointment”, marked by many failures to find antibodies made by a person’s body against their own hypocretin. “It’s one of the biggest things to happen in the narcolepsy field for some time.”
Loose ends
It is not clear why some people make these T cells and others do not, but genetics may play a part. In earlier work, Mignot showed that 98% of people with narcolepsy have a variant of the gene HLA that is found in only 25% of the general population.
Environmental factors, such as infections, probably matter too. Mellins’ working model is that narcolepsy happens when people with a genetic predisposition, which involves having several narcolepsy-related gene variants, encounter an environmental factor that mimics hypocretin, triggering a response from the immune system. The 2009 H1N1 virus was one such trigger: the team found that these same special CD4+ T cells also recognize a protein from the pandemic H1N1 virus.
Narcolepsy of course was around long before the 2009 pandemic. And since new cases of the disease tend to arise right after winter — following the seasonal peak in flu — it’s possible that other strains or even other viruses are involved, too.
But the results do not fully explain the Pandemrix mystery, because other flu vaccines contained the same proteins but did not lead to a spike in narcolepsy cases. Regardless, Mellins says that it should be possible to avoid repeating the same mistake by ensuring that future flu vaccines do not contain components that resemble hypocretin.
Another loose end is that “they don’t show how these T cells are actually killing the hypocretin neurons”, adds Scammell. “It’s like a murder mystery and we don’t know who the real killer is.” He thinks that it is unlikely that the T cells are the true culprits; instead, they could be acting through an intermediary, or might merely be a symptom of some other destructive event.
“The results are very important, but they need to do a replication study in a large group of patients and controls,” says Gert Lammers, a neurologist at Leiden University Medical Center in the Netherlands and president of the European Narcolepsy Network. “If the findings are confirmed, the first important spin-off might be the development of a new diagnostic test.”
New biological links between sleep deprivation and the immune system discovered
Population-level studies have indicated that insufficient sleep increases the risk of cardiovascular diseases and type 2 diabetes. These diseases are known to be linked to inflammatory responses in the body.
University of Helsinki researchers have now shown what kinds of biological mechanisms related to sleep loss affect the immune system and trigger an inflammatory response. They identified the genes which are most susceptible to sleep deprivation and examined whether these genes are involved in the regulation of the immune system. The study was published in the journal PLOS ONE on October 23, 2013.
Conducted at the sleep laboratory of the Finnish Institute of Occupational Health, the study restricted the amount of sleep of a group of healthy young men to four hours per night for five days, imitating the schedule of a normal working week. Blood samples were taken before and after the sleep deprivation test. White blood cells were isolated from the samples, and the expression of all genes at the time of the sampling was examined using microarrays. The results were compared with samples from healthy men of comparable age who had been sleeping eight hours per night for the week.
"We compared the gene expression before and after the sleep deprivation period, and focused on the genes whose behaviour was most strongly altered," explains researcher Vilma Aho. "The expression of many genes and gene pathways related to the functions of the immune system was increased during the sleep deprivation. There was an increase in activity of B cells which are responsible for producing antigens that contribute to the body’s defensive reactions, but also to allergic reactions and asthma. This may explain the previous observations of increased asthmatic symptoms in a state of sleep deprivation."
The amount of certain interleukins, or signalling molecules which promote inflammation, increased, as did the amount of associated receptors such as Toll-like receptors (TLR). On the gene level, this was apparent in the higher-than-normal expression of the TLR4 gene after sleep loss. CRP level was also elevated, indicating inflammation.
The researchers also wanted to examine the impact that long-term sleep deprivation could have on the immune system. For this follow-up study, they used material from the national FINRISKI health survey. Participants in this population study underwent blood tests but also answered questions about their health, for example whether they were getting enough sleep.
The researchers compared participants who believed they were sleeping sufficiently with those who felt that they were not sleeping enough. Some of the gene-level changes observed in the experimental working week sleep restriction study were repeated in the population sample. These results may help explain the connection between shorter sleep and the development of inflammatory diseases, such as cardiovascular disease and diabetes, which has been established in epidemiological studies.
"These results corroborate the idea that sleep does not only impact brain function, but also interacts with our immune system and metabolism. Sleep loss causes changes to the system that regulates our immune defence. Some of these changes appear to be long-term, and may contribute to the development of diseases that have been linked to sleep deprivation in epidemiological research,” Aho states.
Boost your Immune System and Shake Off Stress by Taking a Walk in the Woods
Work, home, even in the car, stress is a constant struggle for many people. But it’s more than just exhausting and annoying. Unmanaged stress can lead to serious health conditions such as high blood pressure, heart disease, obesity and diabetes.
“The American lifestyle is fast-paced and productive, but it can be extremely stressful. If that stress is not addressed, our bodies and minds can suffer,” said Dr. Aaron Michelfelder, professor of Family Medicine at Loyola University Chicago Stritch School of Medicine.
Our bodies need sleep to rejuvenate and if we are uptight and stressed we aren’t able to get the rest we need. This can lead to serious physical and mental health issues, which is why it’s extremely important to wind down, both body and mind, after a stressful day.
According to Michelfelder, one of best ways to unwind and reconnect after a stressful day is by taking a walk. Though any walking is good, walking in the woods or in nature has been proven to be even better at reducing stress and improving your health.
“When we get to nature, our health improves,” Michelfelder said. “Our stress hormones rise all day long in our bloodstream and taking even a few moments while walking to reconnect with our inner thoughts and to check in with our body will lower those damaging stress hormones. Walking with our family or friends is also a great way to lower our blood pressure and make us happier.”
Research out of Japan shows that walking in the woods also may play a role in fighting cancer. Plants emit a chemical called phytoncides that protects them from rotting and insects. When people breathe it in, there is an increase in the number of “natural killer” cells , which are part of a person’s immune response to cancer.
“When we walk in a forest or park, our levels of white blood cells increase and it also lowers our pulse rate, blood pressure and level of the stress hormone cortisol,” Michelfelder said.
He also suggests reading, writing, meditating or reflecting to help calm the mind after long day. To help calm the body yoga and breathing exercises also are good.
“If you want to wind down, stay away from electronic screens as they activate the mind. Electronic devices stimulate brain activity and someone’s post on Facebook or a story on the evening news might cause more stress,” Michelfeder said.
Researchers Uncover 48 New Genetic Variants Associated with Multiple Sclerosis
Study brings to 110 known risk factors and provides important insight into disease mechanism
Scientists of the International Multiple Sclerosis Genetics Consortium (IMSGC) have identified an additional 48 genetic variants influencing the risk of developing multiple sclerosis. This work nearly doubles the number of known genetic risk factors and thereby provides additional key insights into the biology of this debilitating neurological condition. The genes implicated by the newly identified associations underline the central role played by the immune system in the development of multiple sclerosis and show substantial overlap with genes known to be involved in other autoimmune diseases.
Published online September 29 in the journal Nature Genetics, the study, “Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis,” is the largest investigation of multiple sclerosis genetics to date. Led by the University of Miami Miller School of Medicine, this study relied upon an international team of 193 investigators from 84 research groups in 13 countries and was funded by more than 40 local and national agencies and foundations.
Multiple sclerosis (MS) is a chronic disabling neurological condition that affects over 2.5 million individuals worldwide. The disease results in patchy inflammation and damage to the central nervous system that causes problems with mobility, balance, sensation and cognition depending upon where the damage to the central nervous system occurs. Neurological symptoms are often intermittent in the early stages of the disease but tend to persist and progressively worsen with the passage of time for the majority of patients. The risk of developing multiple sclerosis is increased in those who have a family history of the disease. Research studies in twins and adopted individuals have shown that this increased risk is primarily the result of genetic risk factors.
The findings released in this study nearly double the number of confirmed susceptibility loci, underline the critical role played by the immune system in the development of multiple sclerosis, and highlight the marked similarities between the genetic architecture underlying susceptibility to this and the many other autoimmune diseases.
The present study takes advantage of custom designed technology known as ImmunoChip—a high-throughput genotyping array specifically designed to interrogate a targeted set of genetic variants linked to one or more autoimmune diseases. IMSGC researchers used the ImmunoChip platform to analyze the DNA from 29,300 individuals with multiple sclerosis and 50,794 unrelated healthy controls, making this the largest genetics study ever performed for multiple sclerosis. In addition to identifying 48 new susceptibility variants, the study also confirmed and further refined a similar number of previously identified genetic associations.
With these new findings, there are now 110 genetic variants associated with MS. Although each of these variants individually confers only a very small risk of developing multiple sclerosis, collectively they explain approximately 20 percent of the genetic component of the disease.
Explaining the significance of the work and the nature of the collaboration, the Miller School’s Jacob McCauley, Ph.D., who led the study on behalf of the IMSGC, said, “With the release of these new data, our ongoing effort to elucidate the genetic components of this complex disease has taken a major step forward. Describing the genetic underpinnings of any complex disease is a complicated but critical step. By further refining the genetic landscape of multiple sclerosis and identifying novel genetic associations, we are closer to being able to identify the cellular and molecular processes responsible for MS and therefore the specific biological targets for future drug treatment strategies. These results are the culmination of a thoroughly collaborative effort. A study of this size and impact is only possible because of the willingness of so many hard working researchers and thousands of patients to invest their time and energy in a shared goal.”
(Source: med.miami.edu)