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Womens immune system genes operate differently from men’s

Women’s immune system genes operate differently from men’s

A new technology reveals that immune system genes switch on and off differently in women and men, and the source of that variation is not primarily in the DNA.

Jul 29 2015

Howard Chang

Howard Chang and his colleagues have developed a technology that enables to sample living cells in real time to better understand how they operate.
Steve Fisch

A new technology for studying the human body’s vast system for toggling genes on and off reveals that genes associated with the immune system toggle more frequently, and those same genes operate differently in women and men.

Some genes are virtually always on, like the clock light on a microwave; others sit unused for years at a time, like some regrettable appliance you bought, stuffed into the back of the closet and forgot. Some genes can be always on in one person and always off in another. A minority of genes switch on and off, like a favorite cell phone app. A new technology, which makes it possible to study the molecules that regulate all of that switching in living people as they go about their lives, has revealed some intriguing surprises, according to a study from the Stanford University School of Medicine.

One of those discoveries is that the genes that switch on and off differently from person to person are more likely to be associated with autoimmune diseases. Another is that women and men use different switches to turn on many immune system genes. It’s too soon to be sure, but that difference in activity might explain the much higher incidence in women of autoimmune diseases such as scleroderma, lupus and rheumatoid arthritis.

“Part of why this is possible is a new technology that was invented at Stanford for measuring the accessibility of the genome to regulatory elements,” explained the study’s senior author Howard Chang, MD, PhD, professor of dermatology.

The new technique, called ATAC-seq and developed by Chang’s team, lets researchers sample living cells in real time to see what they are up to. “In the past,” he said, “people needed a huge number of cells to do this kind of measurement. You’d actually need a pound of flesh to get certain rare cell types. So you can’t get that out of a live person — and certainly not more than once, right?”

Examining the source

Researchers coped by growing cells in the lab, so they had enough cells to study. “But now,” continued Chang, “you are studying copies of copies; you aren’t studying the original cells anymore. Those months of being grown in the lab completely changes how the cells are behaving and so you are no longer looking at the personal. How the laboratory cells behave has nothing to do with what the person just ate, whether they had a fight with their girlfriend or whether they had an infection,” said Chang. With lab-grown cells, the cells haven’t experienced any of those things, all of which can alter the regulation of individual genes.

The new study, published July 29 in the new journal Cell Systems, took ordinary blood samples from 12 healthy volunteers to measure how certain genes are switched on and off, and how that measure varied from individual to individual. Chang’s team also looked at how much change occurred at different times in the same volunteers. The researchers looked exclusively at specialized immune cells called T cells, which are easy to isolate from a standard blood test, easy for volunteers supply and an important component of the immune system.

The single greatest predictor for genes’ tendency to turn on and off was the sex of the person.

One goal of the study was to establish a baseline measure of how much this gene-switching activity varies among healthy people. That way, when other researchers make similar measures in people who are ill, they’ll have an idea of what is normal. Another goal was to refine the new technique for measuring gene activity in standard blood samples.

“We were interested in exploring the landscape of gene regulation directly from live people and look at differences,” said Chang. “We asked, ‘How different or similar are people?’ This is different from asking if they have the same genes.” Even in identical twins, he said, one twin could have an autoimmune disease and the other could be perfectly well. And, indeed, the team reported that over a third of the variation in gene activity was not connected to a genetic difference, suggesting a strong role for the environment. “I would say the majority of the difference is likely from a nongenetic source,” he said.

The sex factor

Across the 12 healthy volunteers, 7 percent of the genes were switched on in different patterns from person to person. For each person, these patterns persisted over time, like a unique fingerprint. “But the single greatest predictor for genes’ tendency to turn on and off was the sex of the person. In terms of significance,” said Chang, “sex was far more important than all the other things we looked at, perhaps even combined.” When the team measured gene activity levels from 30 of the top 500 genes the researchers expected would show gender-influenced activity, they found that 20 of the 30 genes showed significant differential activity between men and women.

Chang directs the Center for Personal Dynamic Regulomes at Stanford University, which aims to map the “regulome” — the complete set of all the switches that turn genes on and off in real time.

Other Stanford-affiliated authors of the paper are Kun Qu, PhD, senior research associate; Lisa Zaba, MD, PhD, instructor of dermatology; Paul Giresi, PhD, former postdoctoral scholar; Rui Li, life science research assistant; Michelle Longmire, MD, clinical instructor of dermatology; Youn Kim, MD, the Joanne and Peter Haas Jr., Professor for Cutaneous Lymphoma Research; and William Greenleaf, PhD, assistant professor of genetics.

This work was supported by the National Institutes of Health (grants P50HG007735 and U19AI110491), the Howard Hughes Medical Institute, the Stanford Cancer Center, the Scleroderma Research Foundation and the Haas Family Foundation.

Information about Stanford’s Department of Genetics, which also supported the work, is available at http://genetics.stanford.edu.



Stanford Medicine integrates research, medical education and health care at its three institutions – Stanford University School of Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children’s Hospital Stanford. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu.

The intent of this site is to help others through sharing information.  Kelly Helsel does not endorse or intend to mislead any readers as to the content of any articles or books on this site.

 

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MS and Mood Swings!!!!!

Understanding and Managing Multiple Sclerosis Mood Swings

You’re happy one minute and angry the next. A television commercial might bring you to tears, or you’re suddenly snapping at others for no reason. These are all examples of mood swings, which are common in people with multiple sclerosis (MS).

In MS, the immune system attacks the protective covering (myelin) that coats the nerves of the central nervous system (CNS), creating lesions or scars. The brain, spinal cord, and optic nerve all make up the CNS. Depending on what part is involved, a wide range of symptoms can result. Mood swings are one of the many symptoms common to MS, but the connection between the disease and emotions often goes unrecognized.
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While it’s easy to see the physical effects of MS, such as balance, trouble walking, or tremors, the emotional impact of the disease is not so apparent. MS can involve various types of emotional instability, including uncontrollable laughing and crying or even euphoria. However, you can manage your mood swings with treatment, therapy, and frank communication.
Pinning Down the Cause

MS mood swings can strike without warning and leave a person with MS feeling frustrated and overcome by their seeming lack of emotional control. It’s important to understand what you’re feeling and try to understand the reasons for emotional swings. You might benefit from talking about your feelings with others. Being as honest and observant as possible will help in determining the cause.

Some common reasons for MS-related mood swings include:

stress
depression
pent-up frustration
anxiety
inability to cope
grief

Besides external factors, the disease itself may play a role in mood swings. Many patients report a worsening of their emotional symptoms during an MS attack.

There are two parts of the brain involved in emotion. One part forms emotional responses, while the other allows you to control them. MS lesions can form in the part of the brain that allows you to control emotions. This might lead to difficulties with self-control. It can also cause unbalanced expressions of sadness or happiness.

Emotional responses can even be scrambled, causing you to laugh at sad news or cry at something funny.
Dealing with Cognition Changes

The first step in taming MS mood swings is to communicate with your neurologist. A neurologist or mental health expert can give you tools to conquer your emotional roller coaster. Some people find counseling helpful, while others manage their emotions with mood-stabilizing drugs, anti-anxiety medication, or antidepressants.

In addition to therapies, you can take these proactive steps to control your moods:

Delegate. If you’re overwhelmed by your daily routine, reduce stress by delegating some tasks. Free yourself from burdens in order to relax and focus.
Turn to a friend. Find a friend to confide in about frustrations or fears. Just talking can help release pent-up feelings. This can keep your emotions from boiling over in the form of a mood swing.
Find support. Join an MS support group. Talking things out with others who are going through a similar experience can help. The group leader can also provide resources to find experts who can help.
Practice peace. Practice yoga or mindful meditation. The calming effects of yoga and meditation can help your brain settle down and focus.
Explain. Tell others about your mood swings before they happen. Sometimes the worry of what others might think can cause enough stress to bring on an event. Letting others know it’s part of your disease will ease your mind.
Breathe. Deep breathing can calm you down and give you an extra moment to take back control when you find yourself in a stressful situation.
Think it through. If you pause and examine your feelings objectively, you may be able to reclaim control. Realizing what is triggering your emotions can also help.
Exercise. Physical exercise has been shown to have a positive effect on mental well being. Besides being good for your body, the time you spend engaged in exercise can be a great time for personal reflection.

There Is Help

Remember that mood swings are common in MS. They shouldn’t be reason for shame or embarrassment, but they shouldn’t be ignored either. Reach out to your neurologist or primary care doctor and let them know that you’re experiencing anxiety, depression, sadness, or even inappropriate bursts of laughter. They can refer you to a mental health specialist who is trained to identify and help you manage the emotional mood swings of MS.

Therapists or counselors are trained to recognize and help you see what flips your emotional “switch.” A mental health professional can give you tools to take emotional control. If your relatives are affected by your mood swings, family counseling can also be beneficial.

If medication is in order, you can work together with your doctor to weigh the risks and benefits of each and find the one that’s right for you.

With all the help available to treat the emotional symptoms of MS, there is no reason for you to suffer in silence. The right combination of counseling and medication will help you feel like yourself

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The intent of this site is to help others through sharing information.  Kelly Helsel does not endorse or intend to mislead any readers as to the content of any articles or books on this site.

 

 

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