Tag Archives: immunology

NIH scientists identify a genetic disorder that may affect 1 in 20

[Mast cells from a sinus stained in blue. Image via Wikimedia Commons & CC 2.0] 

On July 10, 2010, a DC restauranteur came down with what seemed to be food poisoning. He had no energy and no appetite. Rashes flared up. He could barely get out of bed. First hours and then days dragged by without any relief from the symptoms.

The restauranteur’s family sought out doctor after doctor, until finally they were referred to a lab at the NIH (National Institutes of Health) that studies how allergies pass down through families. 

His symptoms fit a diagnosis of Mast Cell Activation Syndrome, (MCAS)  a disorder where a type of immune cells called mast cells release chemicals that send other immune cells into a destructive frenzy. Ideally, mast cells detect infection and spur other immune cells into action. However, some people’s mast cells have a hair trigger. When mast cells release their chemical contents too often, immune cells end up attacking healthy tissue, causing allergies, stomach issues, and heart palpitations. 

[Above: An NIH-produced video about MCAS and Milner’s research into mast cell activation genetics.] 

Unfortunately, most treatments for MCAS aim at the symptoms, not the root cause.  But the NIH team delved deeper into the genetics and found a pattern:  many MCAS-related symptoms run in families.

And oddly enough, hyperflexible joints, dysautonomia, and baby teeth that fail to fall out also ran in many of those families. Many of these symptoms skipped generations, only showing up occasionally in individuals. But genetic sequencing revealed the correlation wasn’t coincidence.

In October, NIH scientist Joshua Milner and his team described the  genetic disorder in a paper in Nature Genetics. According to the team’s paper, 4-6% of the U.S. population has the genes that predispose them to this syndrome–which has been tentatively named alpha-tryptasemia or “alpha-T”.

The symptoms can be cryptic and unrelenting: Dizziness, chronic pain, irritable bowels, fainting. But for many patients with these conditions, there’s no explanation and no treatment. “These [symptoms] are really all triggers to get an eyeroll from a doctor,” said Milner. But for a sizeable portion of population, these seemingly unrelated problems might be part of the previously undiscovered genetic disorder.

Continue reading “NIH scientists identify a genetic disorder that may affect 1 in 20” »

Cachexia: How Cancer Sabotages Patients’ Metabolism

[A cancer patient rests in a hospital bed. Photo by Christine Gleason via Creative Commons 2.0 & Flickr

Tumors are master manipulators. They have to be in order to escape human immune systems. Scientists have found evidence that tumors hide by wearing biochemical disguises and some tumors can even recruit turncoat immune cells to their cause.

And now scientists have found evidence that some tumors alter the whole body’s metabolism by “reprogramming” the liver,  according to a study in the journal Cell Metabolism. [Full disclosure: I have an accepted an internship position at Cell Press’s media relations office, but I don’t start until January. I conducted the interviews this post is based on prior to accepting the internship.] The consequences of that reprogramming are often deadly. 

It’s no secret that many cancer patients waste away. They lose weight, including lean muscle mass.  Many lose their appetites, too. Food doesn’t seem to nourish them anymore. They grow weaker.  Breathing gets harder.  And, too often, they die.

This wasting syndrome is called cachexia.  

“The wasting can get so severe in so many patients that it’s estimated to account for 30% of all deaths due to cancer,” explains study co-author Thomas Flint of University of Cambridge. “Lots of people are saying [the cause of death] is the metastasis; it’s this and that, but about 30% of the deaths don’t seem to be directly explained by the tumor.”  Continue reading “Cachexia: How Cancer Sabotages Patients’ Metabolism” »

Vetting the Spleen: Is it a blood filter or something more?

[Ultrasound of a spleen by Nevit Dilmen via Wikimedia Commons & CC 2.0] 

Blood moves fast.  It only takes about 20 seconds for a red blood cell  to make a full circuit through your entire body, and your blood makes that journey thousands of times each day.

The speed of the blood stream is a challenge for scientists who study how the body copes with invading bacteria. Normally, the bloodstream is devoid of microbial interlopers, but when bacteria do break into the blood stream, they can be extremely dangerous. Sepsis, for example, occurs when the immune system tries to fight off a large number of blood-invading bacteria. And sepsis kills up to half of the people who develop it, according to the NIH

So when bacteria find their way into blood, your body wants to take them out ASAP.  Blood-filtering organs like the liver, the kidneys, and the spleen have dedicated local immune cell task forces that help kill microbes, and of course, blood itself has loads of white blood cells on patrol.

But platelets–the globs of gunk that form scabs on wounds–also trap bacteria. When the bacteria are whizzing through the bloodstream, sometimes they collide with a platelet and get stuck to it. But according to a recent study in Cell Host and Microbe,  getting stuck to a platelet doesn’t kill the bacteria. 

Instead, the platelets carry their trapped bacteria through the bloodstream until they wash up at the spleen, says the study’s senior co-author Admar Verschoor from University of Lubeck in Germany.

Continue reading “Vetting the Spleen: Is it a blood filter or something more?” »

The Case of the Infected Fruit Bats

[Photo  courtesy of Brian Giesen via Creative Commons & Flickr]

“Pitch Imperfect” is a series of blog posts where I highlight stories that I pitched but didn’t quite sell and discuss why it was tough to sell them. The goal is to share both interesting research stories and some of the obstacles in getting them into the news cycle.

Proposed Headline:

How Fruit Bats Spread Ebola and Hendra Viruses Without Getting Sick

Proposed Dek (aka “the sub-headline” or  “social media blurb”)

Unlike most mammalian immune systems which leap into action in response to threats, fruit bats’ immune systems are “on” all the time.

The Pitch (as sent on February 23rd 2016)

Flying foxes– aka fruit bats or megabats— can harbor viruses that are strong enough to tear a human body apart without exhibiting a single symptom.

Or more precisely, while viruses like Ebola and Hendra virus set off violent (and often deadly) immune system chain reactions in humans, fruit bats’ immune systems are able to nip viral infections in the bud right away.

Unfortunately, that means that healthy and highly mobile bats can inadvertently end up transporting viruses like SARS, MERS, Ebola, and Hendra to new locations. However, studying fruit bats’ ability to control viral populations without collateral damage may eventually help humans learn how to coexist with our own volatile immune systems.

Continue reading “The Case of the Infected Fruit Bats” »

HIV Vaccine Origins: New Insight Into League of Extraordinary Immune Cells

[Portrait of an HIV virus by Dominic Alves via Creative Commons & Flickr]

Y’know that feeling when you stumble across a study that makes you think, “Holy s***! Scientists actually did this!!!!”? And then like two weeks later, another team of scientists manages to kind of upstage the first team’s finding?

It’s been that sort of month for HIV vaccine research. A few weeks back, I wrote  about a team of researchers who managed to decrypt the origin story of an extremely effective strain of HIV-fighting antibodies for The Atlantic

I highly recommend reading The Atlantic piece for a full explanation (and also reading The Atlantic’s science and health coverage more generally, because the whole crew over there is pretty awesome)  but here’s the context you need to know:

“Immune cells called B cells build antibodies, tiny protein warheads that seek out and destroy viruses. But because HIV mutates so rapidly, these antibodies are generally ineffective—by the time B cells learn to build antibodies against one version of HIV, a new viral mutant has already taken over.” -me in The Atlantic

B-cells change their antibody designs by mutating at the DNA level. You literally have a team of microscopic mutants protecting your bloodstreams. 

The vast majority of antibodies that those mutant b-cells build suck. But in a few HIV-infected people, the b-cells manage to start building “broadly-neutralizing” antibodies that can disable all sorts of HIV mutants. Researchers love those broadly-neutralizing antibodies (which they’ve nicknamed “Bnabs”) because if researchers could find a way to get HIV-binding bnabs into uninfected people’s blood streams, those people would probably be immune to HIV. 

The Cell paper I wrote up for The Atlantic was a big deal because it marked the first time researchers were able to observe all of the changes that went into transforming an ineffective antibody into an HIV-killing bnab. Then, two weeks later, Science drops this bomb:

Another team of researchers found a way to measure whether individual b-cells have the potential to make a versatile HIV-killing antibody.

Turns out: about 1 in every 700,000 b-cells has the talent.

Continue reading “HIV Vaccine Origins: New Insight Into League of Extraordinary Immune Cells” »

Why scientists aren’t necessarily the best science-explainers

Earlier today, I stumbled across this review of Susannah Cahalan’s Brain on Fire: My Month of Madness, that was written by a neuroscience grad student. I liked the piece, but it got me thinking….

Cahalan was a healthy 24-year-old, working at The New York Post, who suddenly “went mad” and would have almost certainly died, if one of her doctors had not realized that her “madness” may have been the result of a rare auto-immune reaction. Anti-NMDA encephalitis, to be precise.

If you read my review of Molly Caldwell Crosby’s book on encephalitis lethargica (or know anything at all about chronic Lyme disease), you know that anything that causes encephalitis (swelling in the brain) is bad news.

Continue reading “Why scientists aren’t necessarily the best science-explainers” »

Asleep by Molly Caldwell Crosby: A great epidemic history story, up until the last chapter

The book:

Asleep: The Forgotten Epidemic that Remains One of Medicine’s Greatest Mysteries by Molly Caldwell Crosby (2010)

What it’s about:

Asleep is the story of the encephalitis lethargica epidemic that followed in the wake of the 1918 flu. Encephalitis lethargica is mainly known by the nickname “Sleeping Sickness”, but shouldn’t be confused with African trypanosomiasis, a tsetse-fly-borne malady that also goes by the “Sleeping Sickness” moniker. The two diseases are unrelated (as far as we know) but have vaguely similar symptoms.) It is terrifying.

Each encephalitis lethargica case began with an inocuous sore throat. Most people thought nothing of it at first. But then weird things began. Patients began to fall asleep and not wake up for days or weeks. Or else began to lose motor control of their own bodies. They moved like zombies or puppets on strings. Still others retained normal motor function but began to have uncontrollable violent urges, while remaining completely lucid and logical in normal conversation. (There was one story of a teenaged girl who dug her own eyes out of their sockets with her fingernails and then calmly denied doing any such thing because they had “fallen out during the night”. Otherwise, her behavior was completely rational.)

I couldn’t help but think of the Reavers on Firefly. (If you haven’t seen Serenity, I don’t want to spoil it for you. But seriously? Why haven’t you seen Serenity?)

Asleep follows the doctors and neurologists who tried to help these patients. Their efforts were overshadowed by the 1918 Spanish Flu pandemic, fragmented by war, complicated by the pathogen’s invisibility (whatever caused sleeping sickness couldn’t be isolated under microscopes of the day), and hamstringed by the fact that the symptoms varied so widely, sleeping sickness initially appeared to be several different diseases.

Crosby is working off of case studies from the era, so the overall effect is almost like reading a series of interconnected short stories (featuring some of the same lead detectives). Separately, the chapters are kind of creepy and puzzling, but together they add up into a portrait of the neurology and epidemiology fields in their nascent state.

The Upsides:

It’s incredibly vivid and well researched. My favorite passages in the book actually had nothing to do with science; they were the passages where Crosby describes the bustling streets of 1910s & 1920s New York City. Her descriptions are extraordinarily cinematic, and I loved the way she e presented the history of the disease almost as an anthology of stories based on the original case studies. Plus, it’s just an interesting disease. Creepy, ethereal, & unresolvable. Continue reading “Asleep by Molly Caldwell Crosby: A great epidemic history story, up until the last chapter” »

Viruses can shut down our anti-viral proteins – Recap of talk by Dr. Ileana Cristea

The Talk:

Host Defense and Viral Immune Evasion: A Proteomics Perspective

In Plain English:

Human cells and viruses are locked in a protein-based arms race for global domination: Will the cell’s defensive proteins successfully recognize viral DNA and alert the immune system? Or will the virus counter with proteins that stop the defensive proteins in their tracks? The answer is that both of these processes are happening all the time.

The Speaker:

Ileana Cristea of Princeton University’s Molecular Biology Department

The Location:

Harvard Medical School’s Microbiology & Immunobiology department

What it covered:

Full disclosure: I got to the talk about 10 minutes late after being stopped by a security guard (who wasn’t sure how to react to a 22-year-old with a backpack who could speak proteomics-babble but couldn’t produce a student ID). So I missed the first few slides of the talk, but when I arrived, Dr. Cristea was introducing the HMS research crowd to Gamma-Interferon-Inducible Protein 16 (IFI-16) and its role in the innate immune system. Continue reading “Viruses can shut down our anti-viral proteins – Recap of talk by Dr. Ileana Cristea” »

Epidemic of Absence: A book that made me think too much

What it’s about:

Moises Velasquez-Manoff’s Epidemic of Absence tackles one of the trickiest and trendiest topics in 21st-century biomedical research: the complex relationship between autoimmune disease and the bacteria that live in our guts.

A growing body of evidence suggests that by decimating the number of pathogenic microbes people are exposed to, modern medicine has inadvertently shifted the ecological balance between the human immune system and the human microbiome, leaving millions of people vulnerable to allergies and autoimmune disease.

The basic evolutionary argument is that our immune system evolved to cope with a constant onslaught of opportunistic microbes by developing a complex system of checks-and-balances with our bodies’ microbial populations. With those microbes gone, many of the immune system’s coping strategies are having disastrous side effects. In this book, Velasquez-Manoff implicates the depletion of bacterial biodiversity as a driving agent in the pretty much every non-infectious disease you can think of (cancer, depression, Crohn’s, Celiac’s, allergies, and autism are all covered in this book).

The Upsides:

It’s a rare snapshot of a scientific revolution in progress. And it’s easily the most thought-provoking book I’ve read all year. Continue reading “Epidemic of Absence: A book that made me think too much” »