Fine-Tuning Cells to Tune Out Disease: Immune System Discoveries Spur Hope

To understand what causes type 1 diabetes (T1D), imagine a spy novel. It starts with a hero, the T-cell, that roams your body like James Bond. The T-cell hunts down enemies — bacteria and viruses — and snuffs them out. Then something goes terribly wrong: The hero becomes a villain.

Like a double agent, T-cells can turn against your body and attack your pancreas, triggering T1D. It keeps attacking for years, methodically destroying your ability to produce insulin and control blood sugar. Your T1D becomes ever more debilitating.

Fortunately, there’s hope: One of Benaroya Research Institute’s real-life heroes, Alice Long, PhD, is moving closer to a therapy that makes the enemy T-cells so exhausted they surrender.

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BRI researcher Alice Long, PhD

“We think it could be possible to make the T-cells say ‘we give up, we’re too tired to keep attacking the pancreas,’” Dr. Long says. “That could slow down T1D or maybe even stop it.”

This approach of manipulating T-cells to stop disease could extend far beyond T1D. That’s why Dr. Long is teaming up with other BRI researchers, including BRI President Jane Buckner, MD, to study the machinery inside these cells more closely than ever before.

“This could reveal ways to dial T-cells down to stop autoimmune disease, or dial them up so they attack cancer,” Dr. Buckner says. “It’s a new frontier of immune research and BRI is excited to be at the forefront.” 

T-cell Discoveries

Dr. Long has dedicated her career to finding better therapies for the millions of people with T1D. The best available treatment is to inject insulin. Even then, T1D increases the risk of serious health issues like heart disease and stroke.

“There’s a desperate need for therapies that protect the pancreas so it can keep producing natural insulin, because that helps people with T1D stay healthier and have fewer complications,” Dr. Long says.

Dr. Long believes that understanding a phenomenon called “T-cell exhaustion” could unlock these therapies. Several years ago, researchers discovered the body is home to exhausted T-cells, which are alive but have stopped attacking. Everyone has these exhausted cells. But subsequent research showed that people with autoimmune disease who have higher numbers of these cells also have less severe disease and fewer complications. Then Dr. Long and Peter Linsley, PhD, made a key discovery of their own.

They showed that T1D progresses more slowly in people who have higher numbers of exhausted CD8 T-cells. They also found that a drug called teplizumab increased exhausted CD8 T-cells in most individuals. Even better, BRI researchers led a study that showed treatment with this drug delayed the onset of T1D by approximately three years in people who were susceptible to the disease.

“Those were ‘a-ha moments’ — we started to think, maybe it’s possible to create a therapy that exhausts these cells and stops T1D,” Dr. Long says. “But first we needed to understand these cells in much greater detail.”

Fine-Tuning the Immune System

Dr. Long recently received a $2.6 million National Institutes of Health grant to investigate why CD8 T-cells become exhausted and how this influences T1D. She’s also collaborating with Dr. Buckner and Erik Wambre, PhD, on an NIH-funded project that looks at T-cells in cancer patients.

People with cancer have the opposite problem as people with T1D and other autoimmune diseases. In cancer, T-cells should attack cancer cells, but something about cancer leaves them too exhausted to attack. Drugs called checkpoint inhibitors can nudge those cells back into attack mode. But those drugs can push T-cells into overdrive, until patients end up with symptoms similar to autoimmunity.

“If we can understand the process that leads to autoimmunity in these patients, it could help us understand the biological dial that controls how much T-cells attack,” Dr. Buckner says.

The BRI team’s vision is to be able to control both sides of the T-cell equation. This means they could adjust cancer therapies to prevent autoimmune attacks, or create therapies that exhaust attacker cells and stop autoimmune disease.

“We’re getting closer to being able to turn the immune system up or down depending on a patient’s needs,” Dr. Buckner says, “And that means we’re getting significantly closer to improving the lives of people with everything from T1D to cancer, and maybe even to stopping those diseases altogether.”


A version of this story originally appeared in the Benaroya Research Institute Autoimmune Life Blog

Self-Advocacy for Autoimmune Disease Patients: A Conversation with Judi Rising and Tracey Barnes

Judi Rising and her daughter Tracey Barnes know a lot about advocating for people living with autoimmune diseases. Judi is co-founder of the Autoimmune Advocacy Alliance (A3 Alliance) and has spent years educating local and statewide communities about autoimmune diseases. And Tracey, who has lived with multiple sclerosis (MS) for 11 years, often shared her advice on self-advocacy for autoimmune patients as a former

Judi and Tracey

Judi Rising (left) and her daughter, Tracey Barnes

spokesperson for Biogen. Twenty years ago, however, they knew next to nothing about autoimmune diseases.

Judi and Tracey first learned about autoimmune diseases when Tracey’s brother Pat was diagnosed first with Hodgkin’s disease, then with idiopathic thrombocytopenic purpura (ITP), a rare autoimmune blood disease. Six weeks after his ITP diagnosis, Pat passed away. “We had heard the words ‘autoimmune disease’ prior to this, but had no details of any kind and of course no understanding of the impact it could have,” Judi says.

After Pat’s death, Judi and her husband Dick knew they had to spread awareness about autoimmune diseases. They founded “Pat’s Fund,” to educate others about autoimmune diseases, which grew into the A3 Alliance with the support of Benaroya Research Institute at Virginia Mason. Tracey’s own journey with MS has taught the entire family about what self-advocacy as an autoimmune patient looks like, as well as how family and friends can support loved ones living with one of these 80+ chronic diseases.

We recently sat down with Judi and Tracey to hear their advice on how to advocate for yourself and others living with autoimmune diseases.

Tracey, what does self-advocacy mean to you as a patient living with an autoimmune disease?  

Tracey: Self-advocacy begins with your attitude and how you look at things —attitude is absolutely everything.

What I’ve discovered is that people who’ve been diagnosed with MS go one of two ways. They either say, ‘My life is over and I’m going to give up right now. I don’t care. I’m angry, and I’m scared.’ Or, they say, ‘Okay. This is something that’s in my life, and I’m going to do the best I can to deal with it and move on.’

If I’m having a bad day, I sit down and say, ‘This is what you have—but look at all your blessings, and look at all you’ve been given in life. Are you going to give into this?’ I do not allow myself to go down the slippery slope of thinking about, for example, the fact that I don’t have any children and don’t know who will take care of me when I’m older. Instead of doing that, I think it’s very important to focus on a few things you know will get you out of the darkness.

Self-advocacy is also a process of asking questions and learning. When you don’t understand something about your disease, your medication, or your symptoms, ask the question again.

What does self-advocacy look like at the doctor’s office?

Tracey: No question is dumb—don’t be embarrassed to ask questions. Don’t think, ‘The doctor is going to think I’m dumb, or I’m going to hurt their feelings.’ This is your life. In terms of anything you don’t understand, which is going to be 90 percent of what the doctor tells you, write it down or ask about it. It is so vitally important. For example, when I was first diagnosed, I was given the option to begin taking one of seven or eight different drugs. I didn’t feel prepared to make a choice, but I did. Little did I know the drug that I should have gone on was one that had a huge risk factor—so I had just dismissed it. If I had chosen that drug, I wouldn’t be in the situation I’m in right now [walking with forearm crutches]. If I’d known what I know now, I would’ve said to that nurse, ‘I don’t get it, I don’t know what drug to use. You’ve got to help me.’

Judi: If you have a question that your doctor can’t answer, you can also ask for a referral to a specialist or a system with specialists, like Virginia Mason or the University of Washington. We hear story after story about people who are misdiagnosed, sent to the wrong doctor, or not taken seriously by their primary care physician. Don’t be afraid to say ‘I appreciate everything that you’ve told me, and I’d like to hear from someone else. It’s nothing against you, I just want to hear a second opinion.’ There’s nothing wrong with that.

Tracey: It’s also really important to bring someone with you to your appointments. At one point, I took my mom or my husband to all my appointments because they both had a better understanding of the disease, and I wanted a second set of ears. When you start to feel rushed by the doctor, you need to say, ‘I’m feeling rushed. I don’t understand this. When or who can I talk to for more information?’ It’s so important.

How do you build and leverage support networks?

Judi: With regards to building community, support groups look great on the surface but can be really difficult to keep positive. When people don’t have anyone to share their story with, they see a group of people who understand what they’re going through, and sometimes it turns into a gripe session. You have to have someone in the group who helps keep the session positive.

I’ve seen that oftentimes, friends can be even better supporters than family members. It’s perfectly fine to make your support system your friend. If family doesn’t work for you as a support system, seek a friend because they may be more understanding and supportive than your family will. The breakdown of support within families is common, not uncommon. Sometimes, family wants to pretend that the disease is not there.

Tracey: For example, I have a friend who I can call and say, ‘Will you come down to the house and just let me talk?’ And she does. She’s a great friend.

What would you tell people who have been recently diagnosed?

Tracey: I wish there was a way to communicate to people who are newly diagnosed that there is help out there. You can be very positive and keep going in your life. I don’t think that is as well-known as it should be.

Judi: One of the really scary things for a lot of people when they’re first diagnosed is that they go online and get the message, ‘no cures.’ And unfortunately, in most people’s minds ‘no cures’ equates to incurable.

That really isn’t true, in the sense that most autoimmune diseases today do have treatments that can pretty much stop a disease from progressing. If you get on the right path, they can be stopped. And that isn’t exactly the same as incurable.

There are some internet sites that give good information, like Johns Hopkins Autoimmune Research Center’s website, and the Cleveland Clinic’s website as well as their page on understanding autoimmune diseases. In addition, there are some very good books to read like Living Well with Autoimmune Disease by Mary J. Shomon, and The Autoimmune Epidemic by Donna Jackson Nakazawa.

Most importantly, once a person has a diagnosis and a treatment (if available) they should begin to talk with others who have the same disease to find out how they deal with their issues for a better living experience. It is very important for people living with autoimmune diseases to reach out, share, and discuss their experiences.


A version of this story originally appeared in the Benaroya Research Institute Autoimmune Life Blog.

Help Us Learn More about Celiac Disease

Virginia Mason and Benaroya Research Institute are conducting research studies to look closely at the immune system in celiac disease. These studies will be done through a biorepository of blood and tissue samples and medical histories from people with celiac disease.

 People living gluten-free must avoid foods with wheat, rye and barley, found in many foods including bread, pasta and beer.

People living gluten-free must avoid foods with wheat, rye and barley, found in many foods including bread, pasta and beer.

Celiac disease can be difficult to diagnosis and has no cure. The biorepository will allow scientists to study the disease and research novel approaches to the diagnosis and treatment of celiac disease, says Elisa Boden, MD, clinical researcher at BRI who is establishing the Celiac Disease Biorepository.  Dr. Boden is also a gastroenterologist at the Digestive Disease Institute at Virginia Mason Medical Center.

Celiac disease occurs when the immune system attacks the small intestine after exposure to gluten (a protein found in wheat, rye and barley).  This causes inflammation and damage to the small intestine, which can prevent the absorption of water and nutrients into the body. Celiac disease is also known as coeliac disease, celiac sprue, non-tropical sprue, and gluten sensitive enteropathy. Celiac disease is hereditary, meaning that it runs in families. About 1 in 10 people with a first-degree relative with celiac disease (parent, child, sibling) will develop celiac disease.

Celiac disease is estimated to affect 1 in 100 people in the United States and its incidence appears to be rising. In addition, 2.5 million Americans are undiagnosed and may be at risk for long-term health complications. Celiac disease can develop at any age, affecting both children and adults. Left untreated, celiac disease can lead to additional serious health problems. These include nutritional deficiencies, anemia, increased risk of infections, osteoporosis, dermatitis herpetiformis (an itchy skin rash), infertility or miscarriage, neurological conditions including seizures and migraines, and intestinal cancers.

About 1 in 10 people with a first-degree relative with celiac disease (parent, child, sibling) will develop celiac disease.

Currently, the only treatment for celiac disease is lifelong adherence to a strict gluten-free diet. People living gluten-free must avoid foods with wheat, rye and barley, found in many foods including bread, pasta and beer. Gluten is additionally used commonly as a filler in many processed foods. With the increased marketing and development of gluten-free foods, a gluten-free diet has become easier to follow. However, many people with celiac disease still find the diet restrictive and difficult to follow, especially when eating outside their home. In addition, the majority of people with celiac disease continue to demonstrate evidence of ongoing intestinal damage even while attempting to adhere to a strict gluten-free diet. Thus, there is a clear need for adjunctive therapies in the treatment of celiac disease.

There are additionally some people who may have “gluten intolerance” without having celiac disease. These patients may experience symptoms of abdominal pain, bloating, diarrhea or fatigue when they eat a diet containing gluten. While these are common symptoms of celiac disease, these individuals do not have the characteristic small intestinal damage or tissue transglutaminase (tTG) antibodies found in celiac disease. “We do not yet clearly understand what causes non-celiac gluten intolerance,” says Dr. Boden. “Some experts have suggested that many symptoms attributed to gluten intolerance may be caused by FODMAP (Fructose, Olygosaccharides, Disaccharides, Monosaccharides and Polyols)-containing foods that are largely eliminated in gluten-free diets.

“Celiac disease is restricted to people with certain HLA class II genes,” Dr. Boden explains. “About 40 percent of people have these genes but only 1 percent gets the disease. This tells us there are other important genetic or environmental factors that play into the immune reaction in celiac disease. By studying people with celiac disease and healthy people with the same genes, we hope to discover both factors that trigger disease and also those that protect healthy people. We will use this information to develop ways to put the brakes on the immune system to stop it from reacting to gluten. Our hope is to find ways to eliminate the devastating symptoms of this disease and stop damage of the small intestine. ”

Joining the Celiac Disease Biorepository
If you are interested in joining or learning more about the Celiac Disease Biorepository, please call Study Coordinator Kassidy Benoscek at (206) 342-6537, toll-free at  (877) 202-5200 or via email at kbenoscek@benaroyaresearch.org. The biorepository is voluntary. Information is kept confidential, coded with numbers and not names.

For more information visit BenaroyaResearch.org