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Aging, Autoimmune Disease, Immunology, Infectious Disease, Research, Stanford News

Our aging immune systems are still in business, but increasingly thrown out of balance

Our aging immune systems are still in business, but increasingly thrown out of balance

business as usual

Stanford immunologist Jorg Goronzy, MD, told me a few years ago that a person’s immune response declines slowly but surely starting at around age 40. “While 90 percent of young adults respond to most vaccines, after age 60 that response rate is down to around 40-45 percent,” he said. “With some vaccines, it’s as low as 20 percent.”

A shaky vaccine response isn’t the only immune-system slip-up. With advancing age, we grow increasingly vulnerable to infection (whether or not we’ve been vaccinated), autoimmune disease (an immune attack on our own tissues) and cancer (when a once well-behaved cell metamorphoses into a ceaselessly dividing one).

A new study led by Goronzy and published in Proceedings of the National Academy of Sciences, suggests why that may come about. The culprit he and his colleagues have fingered turns out not to be the most likely suspect: the thymus.

This all-important organ’s job is to nurture an army of specialized  immune cells called T cells. (The “T” is for “Thymus.”) T cells are capable of recognizing and mounting an immune response to an unbelievably large number of different molecular shapes, including ones found only on invading pathogens or on our own cells when they morph into incipient tumor cells.

Exactly which feature a given T cell recognizes depends on the structure of a receptor molecule carried in abundance on that T cell’s surface.  Although each T cell sports just one receptor type, in the aggregate the number of different shapes T-cells recognize is gigantic, due to a high rate of reshuffling and mutation in the genes dictating their receptors’ makeup. (Stanford immunologist Mark Davis, PhD, perhaps more than any other single individual,  figured out in the early 1980s how this all works.)

T cells don’t live forever, and their generation from scratch completely depends on the thymus. Yet by our early teens the organ,  situated  in front of the lungs at the midpoint of our chest, starts shriveling up and replaced by (sigh – you knew this was coming)  fat tissue.

After the thymus melts away,  new T-cells come into being only when already-existing ones undergo cell division, for example to compensate for the attrition of their neighbors in one or another immune-system dormitory (such as bone marrow, spleen or a lymph node).

It’s been thought that the immune-system’s capacity to recognize and mount a response to pathogens (or incipient tumors) fades away because with age-related T-cell loss comes a corresponding erosion of diversity:  We just run out of T-cells with the appropriate receptors.

The new study found otherwise.  “Our study shows that the diversity of the human T-cell receptor repertoire is much higher than previously assumed, somewhere in the range of one billion different receptor types,” Goronzy says. “Any age-associated loss in diversity is trivial.” But the study also showed an increasing imbalance, with some subgroups of T cells (characterized by genetically identical  receptors)  hogging the show and other subgroups becoming vanishingly scarce.

The good news is that the players in an immune response are all still there, even in old age. How to restore that lost balance is the question.

Previously: How to amp up an aging immune response, Age-related drop in immune responsiveness may be reversible and Deja vu: Adults’ immune systems “remember” microscopic monsters they’ve never seen before
Photo by Lars Plougmann

Autoimmune Disease, Evolution, Immunology, Microbiology, Nutrition, Public Health, Stanford News

Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?

Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?

hunter-gatherer cafe

Our genes have evolved a bit over the last 50,000 years of human evolution, but our diets have evolved a lot. That’s because civilization has transitioned from a hunter-gatherer lifestyle to an agrarian and, more recently and incompletely, to an industrialized one. These days, many of us are living in an information-intensive, symbol-analyzing, button-pushing, fast-food-munching society. This transformation has been accompanied by consequential twists and turns regarding what we eat, and how and when we eat it.

Toss in antibiotics, sedentary lifestyles, and massive improvements in public sanitation and personal hygiene, and now you’re talking about serious shake-ups in how many and which microbes we get exposed to – and how many of which ones wind up inhabiting our gut.

In a review published in Cell Metabolism, Stanford married-microbiologist couple Justin Sonnenburg, PhD, and Erica Sonnenburg, PhD, warn that modern civilization and its dietary contents may be putting our microbial gut communities, and our health, at risk.

[S]tudies in recent years have implicated [dysfunctional gut-bug communities] in a growing list of Western diseases, such as metabolic syndrome, inflammatory bowel disease, and cancer. … The major dietary shifts occurring between the hunter-gatherer lifestyle, early Neolithic farming, and more recently during the Industrial Revolution are reflected in changes in microbial membership within dental tartar of European skeletons throughout these periods. … Traditional societies typically have much lower rates of Western diseases.

Every healthy human harbors an interactive internal ecosystem consisting of something like 1,000 species of intestinal microbes.  As individuals, these resident Lilliputians may be tiny, but what they lack in size they make up in number. Down in the lower part of your large intestine dwell tens of trillions of  single-celled creatures – a good 10 of them for every one of yours. If you could put them all on a scale, they would cumulatively weigh about four pounds. (Your brain weighs three.)

Together they do great things. In a Stanford Medicine article I wrote a few years back, “Caution: Do Not Debug,” I wrote:

The communities of micro-organisms lining or swimming around in our body cavities … work hard for their living. They synthesize biomolecules that manipulate us in ways that are helpful to both them and us. They produce vitamins, repel pathogens, trigger key aspects of our physiological development, educate our immune system, help us digest our food and for the most part get along so well with us and with one other that we forget they’re there.

But when our internal microbes don’t get enough of the right complex carbohydrates (ones we can’t digest and so pass along to our neighbors downstairs), they may be forced to subsist on the fleece of long carbohydrate chains (some call it “mucus”)  lining and guarding the intestinal wall. Weakening that barrier could encourage inflammation.

The Sonnenburgs note that certain types of fatty substances are overwhelmingly the product of carbohydrate fermentation by gut microbes. These substances have been shown to exert numerous anti-inflammatory effects in the body, possibly protecting against asthma and eczema: two allergic conditions whose incidence has soared in developed countries and seems oddly correlated with the degree to which the environment a child grows up in is spotlessly hygienic.

Previously: Joyride: Brief post-antibiotic sugar spike gives pathogens a lift, The future of probiotics and Researchers manipulate microbes in the gut
Photo by geraldbrazell

Aging, Genetics, Imaging, Immunology, Mental Health, Neuroscience, Research, Women's Health

Stanford’s brightest lights reveal new insights into early underpinnings of Alzheimer’s

Stanford's brightest lights reveal new insights into early underpinnings of Alzheimer's

manAlzheimer’s disease, whose course ends inexorably in the destruction of memory and reason, is in many respects America’s most debilitating disease.  As I wrote in my article, “Rethinking Alzheimer’s,” just published in our flagship magazine Stanford Medicine:

Barring substantial progress in curing or preventing it, Alzheimer’s will affect 16 million U.S. residents by 2050, according to the Alzheimer’s Association. The group also reports that the disease is now the nation’s most expensive, costing over $200 billion a year. Recent analyses suggest it may be as great a killer as cancer or heart disease.

Alarming as this may be, it isn’t the only news about Alzheimer’s. Some of the news is good.

Serendipity and solid science are prying open the door to a new outlook on what is arguably the primary scourge of old age in the developed world. Researchers have been taking a new tack – actually, more like six or seven new tacks – resulting in surprising discoveries and potentially leading to novel diagnostic and therapeutic approaches.

As my article noted, several Stanford investigators have taken significant steps toward unraveling the tangle of molecular and biochemical threads that underpin Alzheimer’s disease. The challenge: weaving those diverse strands into the coherent fabric we call understanding.

In a sidebar, “Sex and the Single Gene,” I described some new work showing differential effects of a well-known Alzheimer’s-predisposing gene on men versus women – and findings about the possibly divergent impacts of different estrogen-replacement  formulations on the likelihood of contracting dementia.

Coming at it from so many angles, and at such high power, is bound to score a direct hit on this menace eventually. Until then, the word is to stay active, sleep enough and see a lot of your friends.

Previously: The reefer connection: Brain’s “internal marijuana” signaling implicated in very earliest stages of Alzheimer’s pathology, The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning, Protein known for initiating immune response may set up our brains for neurodegenerative disease, Estradiol – but not Premain – prevents neurodegeneration in woman at heightened dementia risk and Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women, but not for men
Illustration by Gérard DuBois

Immunology, In the News, Infectious Disease, Parenting, Pediatrics, Public Health

Side effects of childhood vaccines are extremely rare, new study finds

Side effects of childhood vaccines are extremely rare, new study finds

Pneumococcus-vaccineAs you may have heard about elsewhere, a new paper published today on the safety of childhood vaccines provides reassurance for parents and pediatricians that side effects from vaccination are rare and mostly transient. The paper, a meta-analysis appearing in Pediatrics, updates a 2011 Institute of Medicine report on childhood vaccine safety. It analyzed the results of 67 safety studies of vaccines used in the United States for children aged 6 and younger.

“There are no surprises here; vaccines are being shown over and over again to be quite safe,” said Cornelia Dekker, MD, medical director of the vaccine program at Lucile Packard Children’s Hospital Stanford, who chatted with me about the study earlier today. “The safety record for our U.S.-licensed vaccines is excellent. There are a few vaccines for which they document that there are indeed adverse events, but the frequency is quite rare, and in almost all cases they are very easy to manage and self-limited.”

A Pediatrics commentary (.pdf) accompanying the new study puts the value of immunization in context:

Modeling of vaccine impact demonstrates that routine childhood immunizations in the 2009 US birth cohort would prevent ~42,000 deaths and 20 million cases of disease and save $13.5 billion in direct health care costs and $68.8 billion in societal costs.

The commentary goes on to contrast the risks of vaccines with the potential complications of vaccine-preventable diseases:

The adverse events identified by the authors were rare and in most cases would be expected to resolve completely after the adverse event. This contrasts starkly with the natural infections that vaccines are designed to prevent, which may reduce the quality of life through permanent morbidities, such as blindness, deafness, developmental delay, epilepsy, or paralysis and may also result in death.

The study found evidence against suspected links between vaccines and several acute and chronic diseases. For instance, the researchers found high-quality evidence that several different vaccines are not linked to childhood leukemia and that the measles, mumps and rubella (MMR) vaccine is not linked to autism. The DTaP vaccine is not linked to diabetes mellitus, and the Hepatitis B vaccine is not connected to multiple sclerosis, according to moderate-quality evidence.

The evidence does connect a few vaccines to side effects. For instance, the MMR, pneumococcal conjugate 13 and influenza vaccines are linked to small risks of febrile seizures, with the risk of such seizures increasing slightly if the PCV-13 and flu vaccines are given together.

“A febrile seizure can be quite alarming, but fortunately it does not have long-lasting consequences for child,” Dekker said, noting that the risk of such seizures from vaccines is around a dozen per 100,000 doses of vaccine administered.

The rotavirus vaccine is linked to risk of intussusception, an intestinal problem that can also occur with rotavirus infection itself. But the benefits of rotavirus vaccination “clearly outweigh the small additional risk,” Dekker said.

The study confirmed earlier research showing that some vaccines, including MMR and varicella, cause problems for immunocompromised children, such as kids who have HIV or who have received organ transplants. Since they can’t safely receive vaccines, this group of children relies on the herd immunity of their community to protect them.

“It’s not as if the parents of immunocompromised kids have a choice about whether to vaccinate,” Dekker told me. “They have to depend on others to keep immunization levels high, and that starts breaking down when more people hold back from having their healthy kids fully immunized.”

Dekker hopes the new findings will encourage more parents to have their healthy kids fully vaccinated.

Previously: Measles is disappearing from the Western hemisphere, Measles are on the rise; now’s the time to vaccinate, says infectious-disease expert and Tips for parents on back-to-school vaccinations
Photo by Gates Foundation

Cardiovascular Medicine, Immunology, Research, Science, Stanford News, Stem Cells

Oh, grow up! “Specialized” stem cells tolerated by immune system, say Stanford researchers

Oh, grow up! "Specialized" stem cells tolerated by immune system, say Stanford researchers

3075268200_419b9e73b7_zMany of us know by now that stem cells are remarkably fluid in the types of cells they can become. But this fluidity, or pluripotency, comes with a price. Several studies have shown that the body’s immune system will attack and reject even genetically identical transplanted stem cells, making it difficult to envision their usefulness for long-term therapies.

Now Stanford cardiologist Joseph Wu, MD, PhD, and his colleagues have shown that coaxing the stem cells to become more-specialized (a process known as differentiation) before transplantation allows the body to recognize and tolerate the cells. Their research was published today in Nature Communications (subscription required).

From our release:

In a world teeming with microbial threats, the immune system is a necessary watchdog. Immune cells patrol the body looking not just for foreign invaders, but also for diseased or cancerous cells to eradicate. The researchers speculate that the act of reprogramming adult cells to pluripotency may induce the expression of cell-surface molecules the immune system has not seen since the animal (or person) was an early embryo. These molecules, or antigens, could look foreign to the immune system of a mature organism.

Previous studies have suggested that differentiation of iPS cells could reduce their tendency to inflame the immune system after transplantation, but this study is the first to closely examine, at the molecular and cellular level, why that might be the case.

Postdoctoral scholars Patricia Almeida, PhD, and Nigel Kooreman, MD, and assistant professor of medicine Everett Meyer, MD, PhD, share lead authorship of the study. They found that laboratory mice accepted grafts of endothelial cells made from stem cells much more readily than they did the stem cells themselves. As Wu, who also directs the Stanford Cardiovascular Institute said in our release:

This study certainly makes us optimistic that differentiation — into any nonpluripotent cell type — will render iPS cells less recognizable to the immune system. We have more confidence that we can move toward clinical use of these cells in humans with less concern than we’ve previously had.

Previously: New technique prevents immune-system rejection of embryonic stem cells and Overcoming immune response to stem cells essential for therapies, say Stanford researchers
Photo by Umberto Salvagnin

Immunology, Neuroscience, Research, Stanford News

Double vision: How the brain creates a single view of the world

Double vision: How the brain creates a single view of the world

eyes close-upAbout a decade ago, Stanford Bio-X director Carla Shatz, PhD, found that some proteins from the immune system seemed to be playing a role in the brain. Not all scientists were on board with the protein’s double life. Then Ben Barres, MD, PhD, a neurobiologist at Stanford, started finding the same thing with a different set of proteins – these immune system denizens appeared to be functioning in the brain (here’s a write-up on that work by my colleague Bruce Goldman). And still, not all immunologists accepted that the brain might also be using these proteins.

Now Shatz has published a paper online March 30 in Nature that should put the disagreement to rest. She very carefully showed that a protein originally known for its role in the immune system, called MHC Class I D, or D for short, was present in the nerves of the developing brain. She told me, ”The nervous system has just as much right to these immune proteins as the immune system.”

The role D plays is in helping the brain trim back connections as it develops. I didn’t know this before working on my story, but the brain starts out with about double the number of nerve connections than it will eventually use. The ones the brain doesn’t use get trimmed back. Shatz studies this process in a part of the brain that tries to create a single view of the world out of signals coming from the two eyes. In my press release I wrote:

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.

I spoke with Lawrence Steinman, MD, PhD, a neurologist at Stanford who studies multiple sclerosis, a disease of both the immune system and the nervous system. He has a foot in both worlds and has followed Shatz’ work from the beginning. He says part of the problem in gaining acceptance for Shatz’ findings was in a name. A rose by any name may smell as sweet, but a protein with a name like “major histocompatibility complex I” only sounds to a biologist like an immune protein. He says he teaches students that if Shatz had published her work first the protein would have an entirely different name and it would be the immunologists fighting to claim the protein’s role in their world.

“They clearly have major roles in both the nervous system and the immune system,” he said.

Previously: Protein known for initiating immune response may set our brains up for neurodegenerative disorders and Pioneers in science
Photo by Ali Moradmand

Global Health, Immunology, Infectious Disease, Microbiology, Research, Stanford News

Discovered: Why so many people with schistosomiasis (there’s a lot of them) are so vulnerable to bacterial co-infection

Discovered: Why so many people with schistosomiasis (there's a lot of them) are so vulnerable to bacterial co-infection

More than a billion people worldwide – almost all of them in developing countries – are infected by worm-like parasitic organisms called helminths. Organisms making up just a single genus of helminth, Schistosoma, account for one-quarter of those infections, which damage different body parts depending on what schistosomal species is doing the infecting. Some go for the lung. Others (card-carrying members of the species Schistosoma haematobium) head for the urinary tract, with one in ten infected patients suffering severe physical consequences.

People with schistosomiasis of the urinary tract are especially vulnerable to bacterial co-infections. Worse, these co-infections exacerbate an already heightened risk of bladder cancer in infected individuals, it’s believed. Unfortunately, considering the massive numbers of cases, surprisingly little is understood about the molecular aspects of the infection’s course.

A big reason for that relative ignorance has been the absence of an effective animal model enabling the detailed study of urinary-tract schistosomiasis. A couple of years ago, Stanford schistosomiasis expert Mike Hsieh, MD, PhD, developed the world’s first decent mouse model for the disease, allowing him to explore the molecular pathology that occurs early in the course of infection. Now, in a just-published study in Infection and Immunity, Hsieh has put that mouse model to work in coaxing out the cause of the curious collegiality of S. haematobium and co-infecting bacteria.

The secret, the scientists learned, is that S. haemotobium infection induces a spike in levels of a circulating immune-system signaling protein, or cytokine, called IL-4. That excess, in turn, results in a drop in the number and potency of a subset of immune cells that are important in fighting off bacterial infections. The discovery opens a pathway toward the development of new, non-antibiotic drug treatments for co-infected patients that won’t wreak havoc with their microbiomes, as antibiotics typically do.

Previously: Is the worm turning? Early stages of schistosomiasis bladder infection charted, Neglected story of schistosomiasis in Ghana, as told in a  sand animation and A good mouse model for a bad worm

Clinical Trials, Immunology, Pediatrics, Research, Stanford News

Simultaneous treatment for several food allergies passes safety hurdle, Stanford team shows

Simultaneous treatment for several food allergies passes safety hurdle, Stanford team shows

milk and eggsLiving with one food allergy is a challenge; living with more than one can make ordinary activities such as eating at a restaurant feel downright impossible.

That’s because the standard medical advice for the 4 million Americans with food allergies is to avoid all of your allergy triggers, all the time – and, by the way, make sure you always carry injectable epinephrine in case you accidentally eat something contaminated with a food that triggers anaphylactic shock.

So it will be welcome news to these food-allergy sufferers to hear that a Stanford team is making progress on a new way to help them. In research published today in the journal Allergy, Asthma & Clinical Immunology, a team led by Kari Nadeau, MD, PhD, found that an experimental treatment already being widely tested for single food allergies, called oral immunotherapy, could be modified so that patients can be desensitized to multiple food allergens at the same time. The results now being reported are the products of a pair of phase-1 safety trials.

In our press release about the findings, Nadeau explained why she wanted to develop the new therapy:

“Parents came up to me and said things like, ‘It’s great that you’re desensitizing children to their peanut or milk allergies, but my daughter is allergic to wheat, cashews, eggs and almonds. What can you do about that?’” said Kari Nadeau, MD, PhD, associate professor of pediatrics at the medical school and an immunologist at Stanford Hospital & Clinics and Lucile Packard Children’s Hospital Stanford. Nadeau is the senior author of the new study.

… [O]ral immunotherapy is still experimental and quite slow: In prior studies, patients took as long as three years to become desensitized to one food. Being desensitized to several foods, one at a time, could prospectively take decades. Yet Stanford researchers succeeded in safely desensitizing patients to several food allergens at once and were able to speed up desensitization by supplementing oral immunotherapy with injections of omalizumab (brand name Xolair).

With omalizumab, patients were desensitized to up to five of their allergens in a median of 18 weeks; without the medication, the same process took a median of 85 weeks, the research team found. The published results add weight to the anecdotal findings from three of Nadeau’s patients who participated in the trial and shared their experience in a story in the New York Times magazine last spring.

The researchers stress that the treatment is still experimental and must be performed in a hospital setting, but they are excited by the next step in the process: a phase-2 trial to evaluate the therapy more rigorously in a larger number of patients. The phase-2 trial will be conducted at Stanford, where recruitment of new patients has already begun, and at four other centers across the country, which will begin recruiting patients in the coming months. Individuals who are interested in learning more about participating in the new studies can check the federal clinical trials website for opportunities in their region.

Previously: Researchers show how DNA-based test could keep peanut allergy at bay, A mom’s perspective on a food allergy trial and Searching for a cure for pediatric food allergies
Photo by Logan Brumm Photography and Design

Genetics, Immunology, Pediatrics, Research, Stanford News

Researchers show how DNA-based test could keep peanut allergy at bay

Researchers show how DNA-based test could keep peanut allergy at bay

peanut butter cookies

Treating peanut allergy is an arduous process. The only option is a still-experimental therapy, known as oral immunotherapy, in which a patient consumes tiny, gradually increasing doses of peanut powder under a doctor’s supervision. After months or years of treatment, the patient can eat small amounts of peanuts in ordinary foods without provoking an allergic response.

People with severe peanut allergy may think the effort is worthwhile because it frees them from worry that a stray, peanut-containing cookie or stir-fry will trigger anaphylactic shock. But there’s a catch. To maintain this hard-won tolerance, patients who have completed oral immunotherapy are told they must eat peanuts every day for the rest of their lives. If they don’t, they may regain their allergy.

Now, Stanford researchers think they’ve come up with a better option: a potential blood test to see which patients can safely stop eating peanuts without losing their peanut tolerance. A new study led by Kari Nadeau, MD, PhD, found that differences in the DNA of certain white blood cells separated patients who kept their immune tolerance from those who lost it after oral immunotherapy. The study, published today in the Journal of Allergy and Clinical Immunology, followed 20 child and adult patients who completed two years of oral immunotherapy to treat their peanut allergies. They were asked to stop eating peanuts for three months. In that time, 13 regained their sensitivity to peanuts and seven stayed peanut-tolerant.

The researchers saw epigenetic differences between the groups – genetic changes that affect the structure of the chromosome but not the gene sequence itself. The differences could be detected in small blood samples with commonly-available lab equipment, pointing the way to a possible clinical test. FDA approval is needed before the test could be clinically used for this purpose.

From our press release about the study:

“It’s interesting that the change we saw is at the epigenetic level,” Nadeau said, referring to changes in gene activity and expression caused by factors other than DNA sequence. “This might help us tell people if they can safely go off of immunotherapy, or if they need to continue to eat the food every day.” The test could also help researchers determine whether some individuals would benefit from longer courses of immunotherapy, she added.

Interestingly, the new research answers some questions that physicians posed about another just-released study of oral immunotherapy for the treatment of peanut allergies.

Previously: Eating nuts during pregnancy may protect baby from nut allergies, Ask Stanford Med: pediatric immunologist answers your questions about food allergy research and A mom’s perspective on a food-allergy trial
Photo by Muy Yum

Chronic Disease, Immunology, Research, Stanford News

Another piece of the pulmonary-hypertension puzzle gets plugged into place

Another piece of the pulmonary-hypertension puzzle gets plugged into place

puzzle piecePulmonary hypertension, a dangerous increase in the pressure of blood vessels in the lung, is one nasty disease, as I wrote in a Stanford Medicine article a few years ago. As many as three times as many women – many of them quite young – as men are diagnosed with the spontaneous form of PH (which can also arise from scleroderma or bad pharmaceuticals). While an increasing number of pharmaceutical treatments and advocacy groups have made the diagnosis more palatable, there is still no outright cure. Largely, this is because the molecular mechanisms of pulmonary hypertension have remained mysterious.

But recent work has strongly implicated inflammation in pushing predisposed tissues over the edge into the diseased state. And this week, a Journal of Experimental Medicine study led by PH specialist Marlene Rabinovitch, MD, and her colleagues at Stanford’s PH-focused Vera Moulton Wall Center plunks a potentially pivotal piece of the puzzle into place. Rabinovitch and her associates showed that levels of a pro-inflammatory growth factor usually designated by the acronym GM-CSF (if you really must know, it’s “granulocyte-macrophage colony stimulating factor”) rise substantially when a cell-surface receptor with a heavyweight acronym of its own, BMPR2 (for “bone morphogenic protein receptor”) isn’t functioning properly. That can be due to mutations in the gene that codes for the receptor (as occurs in familial versions of PH), to various environmental causes, or the interaction of the two.

Elevated GM-CSF levels in pulmonary tissue work like a siren to call various hot-tempered inflammatory cells to the vasculature of the lung, resulting in thickened vessel walls and commensurately narrowed blood vessels. Conversely, by finding ways to compensate for BMPR2 under-performance, perhaps researchers will be able to develop therapeutics that keep GM-CSF levels within safe limits, modifying the course of incipient PH or even arresting it.

Several million actual and potential sufferers await that Big If with bated breath.

Previously: Researchers reverse pulmonary hypertension in rats by blocking inflammation-producing pathway, New arterial insights portend potential treatments for life-threatening diseases, and Man receives life-saving transplant thanks to health-care reform and a truck
Photo by ePublicist

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