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Autoimmune Disease, Pregnancy, Research, Stanford News, Women's Health

The latest on the pregnancy risks for women with lupus

The latest on the pregnancy risks for women with lupus

2892182827_accf82f274_zWomen with lupus, an autoimmune disorder that can attack a variety of tissues, were once counseled to avoid pregnancy. Now, physicians tailor their advice to each patient’s case. In many instances, however, it’s difficult for physicians to gauge what types of risk their patient might be facing.

A new study designed to clarify those risks found that women with lupus during pregnancy — and even women who may soon be diagnosed with lupus — are more likely to experience preeclampsia, stroke and infection than women without lupus. Infants born to mothers with lupus or pre-lupus are also more likely to be born preterm, have infections, or be small for gestational age, according to the paper, which was published today in Arthritis Care and Research.

“We’ve confirmed previous findings while strengthening the data to show that lupus is associated with a variety of adverse pregnancy outcomes both to the mother, and to the infant,” said senior author Julia Simard, ScD, assistant professor of health research and policy at Stanford.

The research team, which included collaborators in Sweden and at several U.S. universities, examined data from population-based Swedish registers. That data set allowed the researchers to identify patients who had babies several years before being diagnosed with lupus.  From 13,598 single, first-time births, the team identified 551 women with existing lupus and 198 who presented with lupus within five years after giving birth.

For women who have not yet been diagnosed, it’s possible that autoantibodies implicated in the disease may lead to some of the adverse outcomes, but the exact mechanisms remain unknown, Simard said.

She and others are also working to clarify the clinical ramifications of the work, which may help refine physicians’ recommendations and care of pregnant women with lupus, and may lead to earlier diagnoses.

This is a descriptive study, Simard cautioned. Lupus is a challenging condition to study, because it can manifest differently in every patient. As with other chronic diseases, it’s also difficult to distinguish between conditions that could strike anyone, and conditions that might be caused by lupus, she said.

Previously: Empowered is as empowered does: Making a choice about living with lupus, Women and men’s immune system genes operate differently, Stanford study shows Lupus and rheumatoid arthritis may mean fewer children for female patients and Why some autoimmune diseases go into remission during pregnancy
Photo by J.K. Califf

Autoimmune Disease, Immunology, Neuroscience, Research, Stanford News

New perspective: Potential multiple sclerosis drug is actually old (and safe and cheap)

New perspective: Potential multiple sclerosis drug is actually old (and safe and cheap)

new perspectiveAbout 400,000 people in the United States are affected by multiple sclerosis (often referred to by the acronym MS), an autoimmune disorder in which rogue immune cells attack the insulating layer surrounding many nerve cells in the central nervous system.  Some 200 new cases are diagnosed every week in the U.S.

I wrote a while back about a study by Paul Bollyky, MD, PhD, showing that blocking production of a naturally made substance in the body could potentially protect against type 1 diabetes, another autoimmune disorder in which the body’s immune system attacks the pancreas’s insulin-producing cells (the only place where insulin is made). It now appears possible that the same drug Bollyky’s team used to achieve that benefit may also be beneficial in MS.

The substance in question — hyaluronan, a hefty, complex carbohydrate substance — is usually present at trace concentrations in the extracellular matrix that pervades all tissues and, among other things, helps glue those tissues’ constituent cells together. Intriguingly, hyaluronan levels spike markedly at the site of an injury. If you twist your ankle or stub your toe, the swelling you see afterwards is mainly due to hyaluronan, which is prone to soaking up water. That causes fluid buildup, aka swelling,  in the injured region — a cardinal feature of inflammation, along with heat, redness and pain.

In a new study published in Proceedings of the National Academy of Sciences, Bollyky and his colleagues show that hyaluronan also abounds in sites of autoimmune attack in MS patients’ brains after they induced a mousie version of MS in laboratory mice. They confirmed that hyaluronan likewise accumulates near the mice’s MS lesions. And they showed that blocking new hyaluronan synthesis in the mice before symptoms developed prevented many of the mice from succumbing to MS and delayed disease onset and severity in those who did get it, while — importantly — blocking hyaluronan synthesis after symptoms developed alleviated those symptoms.

Perhaps most interesting of all: The drug they used to do that is already on the market for other indications.

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Autoimmune Disease, Chronic Disease

The importance of providing patient support in the face of a life-threatening illness

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; this month’s column comes from Sara Wyen, a survivor raising awareness about the devastating effects of blood clots.

As a long-distance runner, I was accustomed to pain of some sort, primarily in my knee due to a lingering injury that often caused serious pain. So, when I wrapped up a run one Saturday with excruciating left knee pain, I really didn’t think anything of it. But the pain persisted throughout the weekend and was soon accompanied by a stabbing pain in my left side and shortness of breath.

I found out very quickly I most definitely wasn’t alone, but I may have never known without encouragement from my physician

At the urging of my primary care physician, I went to the emergency room and was admitted to the hospital two days later. I had a blood clot in my leg, known as deep vein thrombosis (DVT), and a blood clot in my lung, known as pulmonary embolism (PE). Having never been hospitalized in my life, I was scared, weak, exhausted and in more pain than I had ever experienced. I was put on IV blood thinners and kept in the intensive care unit for several days as doctors monitored my volatile condition due to the blood clot passing dangerously through my heart. I wondered what was happening and whether I would survive.

In the coming days, I was moved to the cardiac unit (the youngest on the floor at just 29 years old) and due to the persistence of one doctor who is now my hematologist, I was diagnosed with antiphospholipid antibody syndrome (APS). I soon learned that APS is an autoimmune condition in which the body mistakenly produces antibodies against itself that contribute to abnormal blood clotting. APS, combined with my use of estrogen-based oral contraceptives, was to blame for my blood clots.

The coming weeks and months of my recovery were the most difficult I’ve ever faced in my life. I could no longer do the things I loved to do, like run, or the things I had to do, like work, and I needed to use an oxygen tank and wheelchair. My strength was depleted, my leg and lungs hurt, and I was grappling with a diagnosis of a lifelong disorder that requires continuous care and medication. I was consumed with unwavering anxiety and depression.

The most frustrating part was that to everyone on the outside, I looked and seemed fine, but I was fighting the biggest battle of my life. I felt betrayed by my body, which I had taken great strides to take care of with healthy eating and exercise. I felt completely isolated by what was happening to me, and doctor support became crucial during the extensive recovery period.

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Autoimmune Disease, Chronic Disease, FDA, Immunology, Pediatrics, Research, Stanford News

Can a safe, cheap pill prevent type 1 diabetes?

Can a safe, cheap pill prevent type 1 diabetes?

happy pillType 1 diabetes, an autoimmune disorder once known as juvenile diabetes because it tends to strike during adolescence or earlier, affects one in every 300 people. With the diagnosis comes the certainty of a lifetime of insulin injections, made necessary due to the destruction of insulin-producing cells in the pancreas by a misguided immune system.

Insulin is a hormone that alerts the body to the presence of glucose in the blood, typically after a meal. In insulin’s absence, the body’s tissues fail to take up glucose, a key energy source. Without several-times-daily insulin shots, type 1 diabetes patients’ blood sugar levels can shoot up to dangerous heights – a condition called hyperglycemia.

There’s never been any way to prevent type 1 diabetes, although it can be predicted based on the detection of self-targeting antibodies in a blood test. But screening for type 1 diabetes this way hasn’t been particularly useful, because there’s been nothing to be done for patients diagnosed in the asymptomatic phase except wait for them to become hyperglycemic and put them on insulin.

Now, an elaborate mouse study by Stanford immunologist and structural biologist Paul Bollyky, MD, PhD, shows that it might be possible to intervene during the asymptomatic stage of type 1 diabetes – using a pharmaceutical compound that’s been on the global market for more than 40 years and has a terrific safety record – thereby stopping the immune system’s stupid but relentless destruction of the pancreas’s vital insulin-producing cells, and stave off hyperglycemia indefinitely.

Bollyky and his colleagues first showed that a particular substance, hyaluronan, builds up near insulin-producing cells in mice developing the murine equivalent of type 1 diabetes, confirming earlier findings in postmortem human pancreatic tissue that had been supplied to Bollyky’s team by the Juvenile Diabetes Research Foundation.

“We wondered what would happen if we prevented that buildup,” Bollyky told me when I interviewed him for my news release on the study. “And we knew a drug that does that.”

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Autoimmune Disease, Genetics, Immunology, Science, Stanford News, Technology

Women and men’s immune system genes operate differently, Stanford study shows

Women and men's immune system genes operate differently, Stanford study shows

A new technology for studying the human body’s vast system for toggling genes on and off reveals that genes connected with the immune system switch on and off more frequently than other genes, and those same genes operate differently in women and men. What’s more, the differences in gene activity are mostly not genetic.

A couple of years ago, geneticists Howard Chang, MD, PhD; Will Greenleaf, PhD, and others at Stanford invented a way to map the epigenome – essentially the real time on/off status of each of the 22,000 genes in our cells, along with the switches that control whether each gene is on or off.

Imagine a fancy office vending machine that can dispense 22,000 different drinks and other food items. Some selections are forever pumping out product; other choices are semi permanently unavailable. Still others dispense espresso, a double espresso or hot tea depending on which buttons you push. The activity of the 22,000 genes that make up our genomes are regulated in much the same way.

That’s a lot to keep track of. But Chang and Greenleaf’s technology, called ATAC-seq, makes it almost easy to map all that gene activity in living people as they go about their lives. Their latest study, published in Cell Systems, showed that the genes that switch on and off differently from person to person are more likely to be associated with autoimmune diseases, and also that men and women use different switches for many immune system genes. That sex-based difference in activity might explain the much higher incidence of autoimmune diseases in women — diseases like multiple sclerosis, lupus and rheumatoid arthritis.

The team took ordinary blood samples from 12 healthy volunteers and extracted immune cells called T cells. T cells are easy to isolate from a standard blood test and an important component of the immune system. With T cells in hand, the team looked at how certain genes are switched on and off, and how that pattern varied from individual to individual. Chang’s team also looked at how much change occurred from one blood draw to the next in each volunteer.

Chang told me, “We were interested in exploring the landscape of gene regulation directly from live people and look at differences. 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.

Previously: Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using
Photo by Baraka Office Support Services

Autoimmune Disease, In the News, Mental Health, Pediatrics, Research, Stanford News

Stanford doctors unraveling mysterious childhood psychiatric disease

Stanford doctors unraveling mysterious childhood psychiatric disease

BrainModel2A story in Sunday’s Wall Street Journal highlights Stanford’s leadership in treating a mystifying disease in which a child suddenly develops intense psychiatric problems, often after an infection. The disease, called pediatric acute-onset neuropsychiatric syndrome, can be terribly disabling, altering kids’ personalities, interfering with their school work and making it hard for families to function.

As the story (subscription required) explains, some physicians question whether PANS is actually a separate disease from the psychiatric diagnoses it resembles, which include obsessive-compulsive disorder and anorexia nervosa. But doctors at Lucile Packard Children’s Hospital Stanford suspect something else is truly going on, likely an autoimmune attack on the brain. The team, led by Jennifer Frankovich, MD, and Kiki Chang, MD, is working to learn more about the disease:

In an effort to establish the science of PANS, the Stanford clinic is collecting extensive data on the patients. Doctors try to piece together what is driving symptoms from pediatric records, parent reports, even teacher interviews. They are analyzing DNA samples from each patient and looking for clues in their immune systems. If they find strep, they bank the strain for further research. “It is easier to study something that is established,” Dr. Frankovich said. “To build something new is really hard.”

The team’s insights from 47 of their patients were published earlier this year in a special PANS-focused issue of the Journal of Child and Adolescent Psychopharmacology, and the researchers are currently working to expand the capacity of their PANS clinic, the first of its kind in the country. More information about PANS and its effect on children and families is also available in a Stanford Medicine magazine story I wrote last year about Frankovich and Chang’s work.

Previously: What happens when the immune system attacks the brain? Stanford doctors investigate and My descent into madness — a conversation with author Susannah Cahalan
Photo by GreenFlames09

Autoimmune Disease, Immunology, Public Health, Research, Sleep, Stanford News

Cause of 2009 swine-flu-vaccine association with narcolepsy revealed?

Cause of 2009 swine-flu-vaccine association with narcolepsy revealed?

syringesBack in 2001, in the wacko cinematic tour de farce “Rat Race,” British actor Rowan Atkinson – a.k.a. the iconic “Mr. Bean” – put a humorous face on narcolepsy, a rare, chronic, incurable and lifelong sleep disorder that can strike at any time, even in the heat of a foot race.

In 2009, narcolepsy suddenly became, for a time, not quite so rare.

The swine flu pandemic sweeping the world that year was no joke. In the United States alone, the H1N1 strain of influenza virus responsible for that pandemic resulted in 274,304 hospitalizations and 12,469 deaths, as mentioned in our news release on a just-published study in Science Translational Medicine.

There probably would have been far more hospitalizations and deaths had not several vaccines tailored to that particular influenza strain been rushed to the market. Two vaccines in particular — Focetria, manufactured by Novartis, and Pandemrix, made by GlaxoSmithKline — are credited with saving a lot of lives in Europe. But there was a dark side. As our news release notes:

Populations that had been immunized with GlaxoSmithKline’s Pandemrix vaccine showed an increase in narcolepsy, but those immunized with Novartis’ Focetria did not.

That’s not news; it’s been known for some time. But the findings in the new study, whose senior author is Stanford neuroimmunologist Larry Steinman, MD, may explain why.

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Autoimmune Disease, Bioengineering, Immunology, Research, Stanford News

Adult humans harbor lots of risky autoreactive immune cells, study finds

Adult humans harbor lots of risky autoreactive immune cells, study finds

dangerIf a new study published in Immunity is on the mark, the question immunologists may start asking themselves will be not “Why do some people get autoimmune disease?” but “Why doesn’t everybody get it?”

The study, by pioneering Stanford immunologist Mark Davis, PhD, and colleagues, found that vast numbers of self-reactive immune cells remain in circulation well into adulthood, upending a long-established consensus among immunologist that these self-reactive immune cells are weeded out early in life in an organ called the thymus.

A particular type of immune cell, called “killer T cells,” is particularly adept at attacking cells showing signs of harboring viruses or of becoming cancerous. As I wrote in my news release about Davis’s study:

[The human immune system generates] a formidable repertoire of such cells, collectively capable of recognizing and distinguishing between a vast array of different antigens – the biochemical bits that mark pathogens or cancerous cells (as well as healthy cells) for immune detection. For this reason, pathogenic invaders and cancerous cells seldom get away with their nefarious plans.

Trouble is, I wrote:

[This repertoire includes] not only immune cells that can become appropriately aroused by any of the billions of different antigens characteristic of pathogens or tumors, but also immune cells whose activation could be triggered by myriad antigens in the body’s healthy tissues. This does happen on occasion, giving rise to autoimmune disease. But it happens among few enough people and, mostly, late enough in life that it seems obvious that something is keeping it from happening to the rest of us from day one.

It’s been previously thought that the human body solves this problem by eliminating all the self-reactive T cells during our early years via a mysterious select-and-delete operation performed in a mysterious gland called the thymus that’s nestled between your heart and your breastbone. Sometime in or near your early teens, the thymus mysteriously begins to shrink, eventually withering and largely turning to useless fat. (Is that mysterious enough for you? It sure creeps me out.)

But Davis and his team used some sophisticated technology – some of it originally invented by Davis, some of it by Stanford bioengineering professor and fellow study co-author Stephen Quake, PhD – to show that, contrary to prevailing dogma, tons of self-reactive killer T-cells remain in circulation well into adulthood. Then the scientists proceeded to explore possible reasons why the immune system keeps these risky cells around (it boils down to: just in case a pathogen from Mars comes along and we need to throw the kitchen sink at it) and why (at least most of the time) they leave our healthy tissues alone: A still-to-be-fully-elucidated set of molecular mechanisms keeps these self-reactive cells locked in the biochemical equivalent of parking gear, shifting out of which requires unambiguous signs of an actual pathogen’s presence: bits of debris from a bacterial cell wall, or stretches of characteristically viral DNA.

That’s our immune system, folks. Complicated, mysterious, and yet somehow incredibly efficient. You really don’t want to leave home – or even the womb – without it.

Previously: In human defenses against disease, environment beats heredity, study of twins shows, Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail, In men, a high testosterone count can mean a low immune response and Deja vu: Adults’ immune systems “remember” microscopic monsters they’ve never seen before
Photo by Frederic Bisson

Autoimmune Disease, Cancer, Infectious Disease, Microbiology, Nutrition, Stanford News

Getting to the good gut: how to go about it

Getting to the good gut: how to go about it

In a blog post a few years ago I wrote, The Good Gutwith misplaced parenthetical self-assuredness:

Anybody who’s ever picked up an M&M off the sidewalk and popped it into his or her mouth (and, really, who among us hasn’t?) will be gratified to learn that the more germs you’re exposed to, the less likely you are to get asthma … hay fever and eczema.

I soon learned to my surprise, if not necessarily to my embarrassment, that virtually nobody – at least nobody over 6 – cops to having stooped-and-scooped as I routinely did as a kid on what I called my “lucky-sidewalk” days.

But those M&Ms may have been the best pills I ever took.

Stanford microbiologists Justin Sonnenburg, PhD, and Erica Sonnenburg, PhD, (they’re married) have written a new book, The Good Gut, about the importance of restocking our germ-depleted lower intestines.

Massive improvements in public sanitation and personal hygiene, the discovery of antibiotics and the advent of sedentary lifestyles have taken a toll on the number and diversity of microbes that wind up inhabiting our gut. According to The Good Gut, we need more, and more varieties, of them. And we need to treat them better. The dearth of friendly microorganisms in the contemporary colon is due not just to a lack of bug intake but to a lack of fiber in the modern Western diet. Indigestible to us, roughage is the food microbes feast on.

The Good Gut packages that message for non-scientists. “We wanted to convey the exciting findings in our field to the general public,” Justin Sonnenberg recently told me. “We’d noticed we were living our life differently due to our new understanding. We were eating differently and had modified both our own lifestyle and the way we were raising our children.”

In simple language, the Sonnenburgs explain how the pieces of our intestinal ecosystem fit together, what can go wrong (obesity, cancer, autoimmunity, allergy, depression and more), and how we may be able to improve our health by modifying our inner microbial profiles. Their book includes everything from theories to recipes, along with some frank discussion of digestive processes and a slew of anecdotes capturing their family’s knowledge-altered lifestyle.

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Autoimmune Disease, Chronic Disease, Health and Fitness, Nutrition, Obesity, Research

Study clarifies link between dieting, exercise and reduced inflammation

Study clarifies link between dieting, exercise and reduced inflammation

4503404991_13da58b6e6_bIf you’ve ever wondered how dieting and exercise reduce inflammation, read on. According to new research, a compound that our bodies crank out when energy supplies are low could be the link between diet and exercise, and reduced swelling in the body.

When diet, fasting and exercise starve the body for calories, the body increases production of a compound called beta hydroxybutyrate (BHB). This compound has long been known as an alternate source of energy; the new research suggests that BHB can also block the inflammatory response.

In their study, published this week in Nature Medicine online (subscription required), a team of scientists co-led by Yun-Hee Youm and Kim Yen Nguyen at the Yale School of Medicine, discovered that the compound BHB reduces swelling in the body by inactivating a group of proteins, called the inflammasome, that drive the inflammatory response.

The research team used human immune cells and mice to explore the effects of BHB in the body. They found that mice given BHB directly, and mice fed a low-carbohydrate diet (that prompted their bodies to synthesize their own BHB), both benefited from reduced inflammation.

These results are noteworthy because a better understanding of the mechanism that links diet, exercise and inflammation could help scientists develop more effective treatments for inflammatory disorders such as Type 2 diabetes, atherosclerosis and Alzheimer’s disease.

Previously: Newly identified type-2 diabetes gene’s odds of being a false finding equal one in 1 followed by 19 zeroesImproving your health using herbs and spices, Exercise may alleviate symptoms of arthritis regardless of weight loss, Study points to inflammation as cause of plaque buildup in heart vessels and Examining the role of exercise in managing and preventing diabetes
Via ScienceDaily
Photo by Dave Nakayama

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