Immunology

Food allergies affect millions of children, who find it difficult to enjoy ordinary activities like birthday parties and restaurant meals because of worries that something they eat could send them into anaphylactic shock. As the New York Times described recently, Stanford scientist Kari Nadeau, MD, PhD, is studying how to desensitize children to their allergy triggers. Here on Scope, she recently took questions on food allergies and her desensitization research.

Many readers asked how they could enroll in Nadeau’s research or in similar allergy treatment trials near their homes. Information for prospective study subjects around the world is available here; enter “food allergy” in the “Search for Studies” field, and after searching, click the “On a Map” tab to see trials grouped by location. For those who live near Stanford, go here for details on participating in Nadeau’s research.

Below are Nadeau’s responses to a selection of questions submitted using the hashtag #AskSUMed the comments section on Scope. As a reminder, Nadeau’s answers are meant to offer medical information, not medical advice. They’re not meant to replace the evaluation and determination of your doctor, who will address your specific medical needs and can make a diagnosis and provide appropriate care.

@vikas_aditya asks: What’s the simplest way to identify the cause of an allergy in kids?

If you suspect an allergy to a specific food or environmental cause, skin prick testing is the simplest and least invasive way to initially identify the allergy but it is not the gold standard. A food challenge in the doctor’s office is the true way to test for food allergies.

Elizabeth P. asks: Is there anyone working to find the exact cause of why so many children, teens and adults are developing life-threatening food allergies today? On a related note, @ceband asks: What do you think of the theory that altered gut microbiomes have led to the rise in allergies and autoimmune disease?

Many scientists and researchers are trying to understand the rising prevalence of food allergies in children. Though there are many theories regarding the increase in this prevalence, we still lack definitive answers. Hypotheses have focused on hygiene, dietary fat, antioxidants, vitamin D and dual-allergen-exposure. Altered gut microbiomes might play a role. It does not appear that genetically modified foods are directly linked to food allergies.

Julie Barnes asks: I am currently pregnant and am wondering if I will possibly be creating a food allergy in my unborn child if I avoid all dairy and egg while pregnant and breastfeeding.

There is recent evidence that a diet in pregnancy and during breastfeeding that is high in Vitamin D, follows features of a Mediterranean diet and includes probiotics may be helpful to prevent asthma and allergies. And a healthy, balanced diet is important to your overall health and the health of your baby. However, we do not have evidence that mothers will create food allergies by food avoidance in pregnancy or breasfeeding. Similarly, there is no evidence from the general population that mothers can create food allergies by eating certain foods during pregnancy or breastfeeding.

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You’ve heard of Sputnik, that little tiny antenna-clad chunk of metal heaved into low orbit on October 4, 1957, effectively kicking off the Space Age?

Well, make way for Gutnik. A news release issued by NASA’s Ames Research Center foretells the launch into space of a satellite inhabited by a bunch of nano-mariners who, left to their own devices, would no doubt rather curl up inside a bowel.

Sometime in the next one to three years, according to the release, a so-called “nanosatellite” weighing about 30 pounds and peopled by the intestinal bug E. coli will streak into the sky, with the mission of amassing data on whether the zero-gravity environment that cloaks our planet might increase microbes’ resistance to antibiotics. That’s important, because, as the release states:

Bacterial antibiotic resistance may pose a danger to astronauts in microgravity, where the immune response is weakened. Scientist believe that the results of this experiment could help design effective countermeasures to protect astronauts’ health during long-duration human space missions.

E. coli is probably the most-studied micro-organism in all of science. While most strains are harmless and actually quite friendly (producing vitamin K for us, just to name one of the nice things they do), some of them can cause food poisoning, urinary-tract infections and more.

Gutnik (whose real name is EcAMSat) is the brainchild of Stanford microbiologist A.C. Matin, PhD, the principal investigator for the joint NASA/Stanford University School of Medicine project. Matin’s previous inventions include microbes capable of gobbling up environmental toxins like uranium and chromium, as well as magnetic-field-seeking bacteria that can increase the contrast of magnetic-resonance imaging. So this new satellite caper is just one more in a series of wild but potentially very useful feats of imagination.

The thing that really knocks me out, though, is how all these scientists and engineers will manage to get those billions of little tiny bugs to sit still while the chin straps on their little tiny space helmets are being fastened.

Previously: Space: A new frontier for doctors and patients and Outer-space ultrasound technologies land on Earth
Photo by Per Olof Forsberg

We’ve written here about the food-allergy work being done by Kari Nadeau, MD, PhD. But what’s it like for the parents of children with severe allergies who participate in one of Nadeau’s trials? As the kids are gradually exposed to foods they are highly allergic to, how do their moms and dads feel? That was the focus today of an NBC online piece, which includes excerpts from e-mails written by a mom of one study participant. A few of the passages jumped out at me:

January 27, 2012: Tessa will officially start the clinical trial at Stanford Hospital Friday morning!

This journey we are about to embark on is a massive one … and not to be underestimated. Not only is the time commitment great … this will be physically and emotionally taxing on Tessa as well. It will be scary for her (and us) at times as she will be reacting to the foods all throughout. Kids can have anything from stomachaches to hives to vomiting, etc.

We were in bed tonight and [Tessa] said “Mommy, I am scared. What if I can’t tell that I am having a reaction and it gets out of control like the last two times when I almost died?” It was a heart-wrenching conversation.

…

February 26, 2012: Tessa is now up to the equivalent of … about one ounce of milk, four peanuts, [and] three whole crackers.

She has now had three home doses at this level and has not even had the slightest reaction (knock on wood) … I watched her eating crackers with her friends the other day … which was a very weird sight to see her eating “normal” food socially like that among friends… and had to make sure that her friends were very clear that she is only able to eat this food because of the drug she is on [Xolair, which suppresses the allergic reaction].

Mentally she is doing very well, too … In fact, she is the one that keeps telling me to “chillax”.

…

April 10, 2012: … There were a few extra M&M’s on the side and Tessa asked me to eat them and I said, “No thank you” and she insisted that I eat them. It was the first time in nine years that I have ever eaten anything “unsafe” in front of Tessa. It was a very odd moment and a feeling that I just don’t think I will ever get used to.

The article accompanied a Today Show segment during which Nadeau talked more about her work. And, as a reminder, she’s taking questions about food allergies this week as part of our Ask Stanford Medicine series.

Previously: Ask Stanford Med: Pediatric immunologist taking questions on children’s food allergy research and Searching for a cure for pediatric food allergies

“Blood is a very special juice.”

Goethe didn’t know the half of it when he penned this line for the character of Mephistopheles, in “Faust,” more than 200 years ago.

In those days people believed blood held mystical qualities and was a potent life force. No wonder Mephisto wants the contract for Faust’s soul signed in the stuff.

But what exactly does blood do?

The new issue of Stanford Medicine magazine tells blood’s story, from 17th-century attempts at blood transfusion to the workings of a modern blood bank to today’s studies of gene therapy to treat hemophilia.

Inside the issue:

• “Blood quest:” An article on Stanford’s early fight to prevent the spread of AIDS by screening blood - while other blood banks argued against testing.
• “Blood, sweat and fears:” The story of a blood phobic and his attempt to conquer the surprisingly common condition.
• “Roll up your sleeve:” An explainer on the irreplaceable resource that is human blood, and why blood donation remains so crucial.
• “Life of blood:” A visual primer on blood cells, the most numerous cells in your body.
• “Against the flow:” A feature on why blood transfusions are declining, and why that’s good news for health.
• “In his blood:” A look at growing up with hemophilia, featuring a physician with hemophilia who is dedicating his life to finding cures for the life-threatening disease.

This issue’s “Plus” section, featuring stories unrelated to the special report, includes:

• “Bubble girl:” A feature on a new treatment for severe combined immunodeficiency disease, also known as “bubble boy disease.”
• “A Nobel experience:” An insider’s view of this year’s Nobel Prize festivities.

Previously: The money crunch: Stanford Medicine magazine’s new special report and The data deluge: A report from Stanford Medicine magazine
Photo by Renphoto

Food allergies among children are a growing public health concern. An estimated six million children in the United States suffer from food allergies, and nearly 40 percent have experienced a severe allergic reaction as a result of consuming a food.

A recent New York Times Magazine story took a closer look at the issue and the research of Kari Nadeau, MD, PhD, a pediatric immunologist at Stanford and Lucile Packard Children’s Hospital. As my colleague previously reported, Nadeau has demonstrated that it’s possible to desensitize children to a single food allergen and is now working to identify treatments to safely address multiple food allergies at the same time.

To continue the conversation, we’ve asked Nadeau to respond to your questions about children’s food allergies and her ongoing projects at the Stanford Alliance for Food Allergy Research. Questions can be submitted to Nadeau by either sending a tweet that includes the hashtag #AskSUMed or posting your question in the comments section below. We’ll collect questions until Friday (March 15) at 5 PM Pacific Time.

When submitting questions, please abide by the following ground rules:

• Stay on topic
• Be respectful to the person answering your questions
• Be respectful to one another in submitting questions
• Do not monopolize the conversation or post the same question repeatedly
• Kindly ignore disrespectful or off topic comments
• Know that Twitter handles and/or names may be used in the responses

Nadeau will respond to a selection of the questions submitted, but not all of them, in a future entry on Scope.

Finally – and you may have already guessed this – an answer to any question submitted as part of this feature is meant to offer medical information, not medical advice. These answers are not a basis for any action or inaction, and they’re also not meant to replace the evaluation and determination of your doctor, who will address your specific medical needs and can make a diagnosis and give you the appropriate care.

Previously: Searching for a cure for pediatric food allergies, Gesundheit! Spring allergy season is underway, New hope for people with severe milk allergies and New insight into asthma-air pollution link
Photo by Steven Depolo

Food allergies affect one in every 13 American kids, yet when a child is diagnosed, modern medicine can’t do much to help. As parents of newly diagnosed kids quickly learn, the standard advice is to avoid allergy triggers completely, since that’s the only surefire way to prevent life-threatening episodes of anaphylactic shock. Many of the common allergy triggers - such as wheat, cow’s milk, soy, eggs and peanuts - are so ubiquitous that avoidance becomes a herculean task. Families have to be extra-cautious about everything from restaurant meals and school events to birthday parties and sleepovers at friends’ homes. In addition to the stress they cause for affected families, food allergies take a big medical toll. They’re responsible for 90,000 episodes of anaphylactic shock each year and 2,000 hospitalizations.

It’s hard enough if your child is allergic to just one food. But a growing number of children have severe allergies to multiple foods. Fortunately, a scientist at Stanford and Lucile Packard Children’s Hospital is working to help these kids. Building on a body of work - her own and others’ - demonstrating that it’s possible to safely desensitize children to a single food allergen, Kari Nadeau, MD, PhD, is now trying to find treatments that will address multiple food allergies simultaneously. Her quest is described in a new feature in this week’s New York Times Magazine:

Could patients be desensitized to more than one allergen at a time? No one had ever tried it, but more than a third of children with food allergies are allergic to more than one food. If it was safe to give patients x milligrams of one allergen, would it be safe to give them one-fifth of x milligrams of five different allergens, as long as the total dose remained the same? That would assume that allergens function in a linear, additive fashion — rather than a multiplicative one; it was also possible that they could interact with one another to produce a more severe reaction.

Nadeau experimented with blood samples of allergic patients and was encouraged to see that the allergens seemed not to interact with one another. She consulted with senior colleagues in the field to see if anyone would collaborate on a multiallergen study, but no one was interested. Scientifically the results would be harder to interpret than single-allergen trials. Moreover, each allergen would require getting separate F.D.A. approval, and it was difficult to get even one application approved. When she found herself home sick in bed with a virus for a few days in 2011, she decided she would “knock them all out” and wrote 13 Investigational New Drug Applications, each 90 or so pages long, and soon received F.D.A. approval for each one.

The entire story is a fascinating behind-the-scenes look at the science of immunology, and well worth reading. Those interested in learning more about Nadeau’s ongoing projects should check out her research group’s website.

Previously: Helping kids cope with allergies, New hope for people with severe milk allergies and Researchers find mechanism for destruction of key allergy-inducing complexes
Photo by Steve Fisch

Biological aging, as opposed to the chronological kind we celebrate or curse annually, is what makes us describe some people as “ageless” and others as “old beyond their years.” We are collections of cells, and what happens in the cell doesn’t stay in the cell. It generates large-scale effects on our overall appearance, health and longevity.

A new study in JAMA indicates that otherwise healthy adults carrying a cellular signature of biological aging may be more vulnerable to infection and, once infected, more likely to exhibit symptoms. The experimenters first drew blood from 152 Pittsburgh residents, none of them over 55 years old, and dosed them with nose drops containing a common cold virus. Monitoring these volunteers for five days, the researchers took note of who sniffled and sneezed and who didn’t, and saw a correlation between study subjects’ susceptibility to the virus and a measure of biological aging called telomere shortening.

Telomeres, which cap the ends of each chromosome in every cell of all living creatures from fungi right on up to humans, are kind of like those plastic caps ringing each end of a shoelace. They stabilize chromosomes, keeping them from unraveling. (They prevent other damage, too.)

But telomeres aren’t so stable themselves. Rounds of cell division, bouts of stress, and episodes of inflammation cause them to shrink. If a telomere reaches a point where a chromosome’s integrity is challenged, the result could be cancer or some other malfunction in the cell housing the challenged chromosome.

Evolution has engineered protective mechanisms into cells so that if their telomeres get too short they die or, at least, lose their ability to divide any more. But this evolutionary emergency brake has its downside: It contributes to the slow but steady deterioration that manifests visibly in our aging skin and, less visibly, in all the other bodily organs.

In this case, the researchers were specifically interested in those bloodborne cells that comprise the immune system. But it’s widely believed that the state of telomeres in blood cells (the cells examined in the study) reflects their state in other tissues as well.

Just a week ago, a study in PLOS ONE led by Stanford psychopharmacologist Natalie Rasgon, MD, PhD, compared the telomeres in blood cells taken from high-functioning, well-educated, apparently fully healthy middle-aged women with a well-known genetic risk factor for late-onset Alzheimer’s disease (a good 15 percent of us are carriers) to those of otherwise matched non-carriers. The first group’s telomeres shortened by as much in two years as the second group’s did in ten, perhaps shedding some light on how this risk factor, called ApoE4, promotes cognitive decline. The good news was that the accelerated telomere shortening seen in ApoE4 carriers wasn’t observed if they’d been on estrogen-based hormone therapy at the onset of menopause and stayed on it for the study’s two-year duration.

While it might be nice to think longer telomeres are all it takes to ensure longevity, even the lengthiest telomeres are no match for a speeding truck. So be sure to look both ways before you cross the street.

Previously: Hormone therapy halts accelerated aging seen in women with Alzheimer’s genetic risk factor, Hormone therapy soon after menopause onset may reduce Alzheimer’s risk and Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s
Photo by ultrakickgirl

Anyone who has ever eaten a rancid food-truck taco has a gut-level feeling for what it’s like to have the human immune system launch a full-scale attack along 30 feet of intestinal tract. Now you can watch this fascinating process at a microscopic level, pain free, thanks to a new animation posted by Nature: Immunology.

Watching it makes me appreciate the amazing complexity of the human immune system. It also serves as a graphic reminder of how much easier it is to understand these processes when you can see them in action.

Readers interested in irritable bowel syndrome might want to skip to minute 4:00, where the animation shows what happens when pathogens sneak past the gut’s protective mucosal barrier. Spoiler alert: Watch out for the “voracious phagocyte” and the “NETosis explosion.”

Previously: The dawn of a new era in microbiology, Study shows intestinal microbes may fall into three distinct categories and A social networking service for digestive health?

Probably no human whose age consists of two digits hasn’t at one time or another experienced a case of deja vu, the uncanny sense of having been through this (whatever “this” may be) before.

Well, it turns out that (as the scary narrator of a kitchy sci-fi TV series I inhaled with both nostrils as a kid might say about UFOs and the like), “We’re not alone…” Our own immune systems, among whose chief functions is to fight off invading pathogens, also entertain “memories” of infectous microbes they’ve never, ever encountered. And that’s a lucky thing.

A human has only 20,000 or so genes, so it’s tough to imagine just how our immune systems are able to recognize potentially billions of differently shaped microbial body parts (or “epitopes” in immune-speak). Stanford immunologist Mark Davis, PhD, tore the cover off of immunology in the early 1980s by solving that riddle.

Now, in a just published study in Immunity, Davis and his team have used an advanced technique developed in his lab in the 1990s to show that a surprising percentage of adult humans’ workhorse immune cells targeting one or another microbial epitope are poised to pounce on the particular epitope they target (and the bug it rode in with) despite having never come across it before. This hypervigilant configuration, called the ”memory” state, was previously supposed to be limited to immune cells that have previously had a run-in with the epitope of interest.

Davis think’s he’s got the dirt on what’s behind the phenomenon: Dirt. He reasons that the kind of immune cells in question have more flexibility than has been thought, so each of them can “cross-react” to a small set of similarly but not identically shaped ”lookalike” epitopes it’s never experienced. Our daily exposures to ubiquitous, mostly harmless micro-organisms that dwell in dirt, on doorknobs, and in our diets gradually produces an aggregate immune “memory” of not only these microbes’ body parts, but those of other bugs as well - including some nasty ones like HIV (the virus that causes AIDS), herpesvirus, and more.

Because cells in the “memory” configuration can react much, much faster to an infectious pathogen than “naive” cells targeting the exact same pathogen, this eerie foreknowledge can spell the difference between life and death.

But this immune memory still depends on having been exposed to something. In the study, the immune cells in blood from newborns’ umbilical cords showed no “memory” of anything at all.

As I wrote in my release on the new findings:

[This discovery] could explain why young children are so much more vulnerable to infectious diseases than adults. Moreover, the findings suggest a possible reason why vaccination against a single pathogen, measles, appears to have reduced overall mortality among African children more than can be attributed to the drop in measles deaths alone.

“It may even provide an evolutionary clue about why kids eat dirt,” Davis told me.

Previously: Immunology escapes from the mouse trap, Age-related drop in immune responsiveness may be reversible and Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s
Photo by Damian Gadal

If there’s one single image that universally connotes death, it’s that of a skeleton. But in the living human body, bones are a beehive of activity that, at the cellular level, is as lively and intricate as any dance troupe could perform.

Within the hollows of the long bones dwells a spongy tissue called marrow, which hosts stem cells responsible for the production of both red and a variety of white blood cells. The latter are the warriors, messengers, sentries and medics that compose our immune system. White blood cells defend against microbial invaders and scour our bodies for suspicious cells showing signs of being cancerous. Without our immune systems we wouldn’t last a week.

Whether white or red, blood cells can become cancerous, giving rise to lymphomas and leukemias that, respectively, account for about 45,000 and 75,000 new cases annually in the United States. One effective method of treating these conditions is bone marrow transplantation. In this procedure, the patient’s own blood-forming stem cells are, as thoroughly as possible, wiped out, and then replaced with bone marrow from a donor. From the new bone marrow springs an entire new, cancer-free immune system.

There are two things to watch out for after a tranplant. The first is the possibility that not every single cancerous blood cell was destroyed. The second is the prospect that the new immune system, perceiving its new home in the patient’s body as foreign tissue, may turn its guns on the patient’s own organs - a condition called graft-versus-host disease, or GVHD.

The better the immunological match between donor and recipient, the smaller the chance of the recipient’s developing the unremitting, chronic, form of this syndrome (cGVHD). But when a male recipient gets bone marrow from a woman, there will always be a set of proteins produced from genes on the man’s Y chromosome that the immune cells from the female donor have never come across, says Stanford bone-marr0w-transplant researcher David Miklos, MD, PhD.

As I wrote in our release concerning Miklos’s recent discovery, just published in Proceedings of the National Academy of Sciences, of a blood-borne biomarker that predicts the onset of cGVHD after female-to-male bone marrow transplants, there’s a trade-off here that often justifies a male leukemia or lymphoma patient’s receiving marrow from a female donor:

While female-to-male bone-marrow transplants put the recipient at 40 percent higher risk of either acute or chronic GVHD than sex-matched transplants, they also reduce the male recipient’s risk of a cancer relapse by 35 percent. Cancer cells are, at heart, unstable and make all kinds of bizarre proteins, fragments of which they tend to display on their surface — a red flag to the immune system. The new immune system is therefore especially vigilant for cancerous cells that somehow survived the effort to destroy them, putting the patient at risk of a relapse.

Miklos has found that the presence of a very particular species of immune cell in the blood of men who’ve received marrow tranplants from women is a strong predictor of impending cGVHD. This early warning that the still asymptomatic condition is developing may may someday allow physicians to administer immune-suppressing drugs that nip cGVHD in the bud.

Previously: Cancer drug shortage implicated in relapses among young Hodgkin lymphoma patients, New leukemia study making waves and Stanford faculty and students launch social media campaign to expand bone marrow donor registry
Photo by Great Beyond