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Graduate School of Biomedical Sciences

GSBS faculty member Pilar Alcaide discusses autoimmune diseases

Wednesday, July 20, 2022

A Tufts Now interview with Pilar Alcaide sheds light on autoimmune diseases and their rise.

If you have celiac disease, inadvertently consuming even a single crumb of bread can lead to gastrointestinal upset for weeks or months. For those who suffer from lupus, a flare can damage kidneys—or even worse. People with rheumatoid arthritis suffer from debilitating joint pain.

They are very different ailments, but all have one thing in common: they are autoimmune diseases, conditions when the body’s immune system attacks not external pathogens but the body itself. Increasingly, researchers are finding other diseases that have a root cause in autoimmune function. Some 24 million Americans are affected by more than 80 autoimmune diseases, according to the National Institute of Environmental Health Sciences, and it seems as if more people are being diagnosed with them than before. Normally, when our bodies are faced with pathogens—such as bacteria or viruses—our immune systems kick into high gear to protect us from these invaders. But sometimes our immune systems confuse parts of our tissues and organs as foreign invaders and attack them instead. The inflammatory response that can knock out an invading bacterium ends up damaging our own health.

Pilar Alcaide, a Kenneth and JoAnn G. Wellner Professor at Tufts University School of Medicine, is an immunologist, focusing on how the immune system impacts cardiovascular health. She also has a personal understanding of these types of diseases. When she was around 6 years old, she was diagnosed with the skin condition psoriasis—an autoimmune disease. It was unusual for a young person to experience the severe psoriasis type she was diagnosed with, and a reminder that these diseases affect all kinds of people.

Tufts Now spoke with Alcaide to learn more about autoimmune diseases, what causes them, who gets them the most, and what can be done about them.

Tufts Now: Do scientists know why this autoimmune response happens?

Pilar Alcaide: There are many different types of autoimmune diseases. A classic one is when there is a mutation on a gene—such as the one that causes Type 1 diabetes. People who have that mutation, their pancreas is attacked by the immune system, with the result that insulin production stops.

Typically autoimmune diseases that are determined by just one gene are developed from birth or from a young age. But for many other autoimmune diseases, genetics is only one part of the cause. For instance, I had severe psoriasis as a child, but most people have mild, moderate, or severe forms of the disease later in life, so it is thought that environment plays a strong role in its development. In many cases, autoimmune diseases develop with age over time, meaning it’s often a combination of genetics, environment, and physiological and mental stress. There’s a lot of research demonstrating that the level of stress plays an important role—the environment and stress. A lot of these autoimmune diseases have flares, when your immune system, for whatever reason, is responding more aggressively than normal.

How does the immune system work normally?

Say a virus or a pathogen hits you. Your body realizes there is a pathogen, and the immune system starts releasing proteins called cytokines. Some of these cytokines will induce fever, which is good—a lot of viruses die at high temperatures. A fever also tells your body that you cannot fight the infection without other internal help. Then other cells called lymphocytes come to help kill the infection. Pro-inflammatory lymphocytes are specialized, and typically they go to where the trigger was.   But then your body needs to turn off the response. When the pro-inflammatory lymphocytes have done their job, anti-inflammatory lymphocytes arrive and suppress the response. Typically, more women than men get autoimmune diseases. But when men get it, it is way more severe than for women.

What happens when it goes haywire in an autoimmune response?

The first barrier of protection to self—our tissues and organs—is what we call immune tolerance. That’s when anti-inflammatory cells recognize, say, “This is a skin protein. It’s OK. You don’t need to respond to that.” That’s homeostasis—the body at equilibrium. But in some cases, a genetic mutation causes a protein to appear that is very similar to something that is part of us, but not quite. Then the inflammatory cells recognize it as a foreign thing, as if it were a pathogen, and they start inflammation. If you are infected with something, you need inflammation, and when you clear that infection, you need anti-inflammation. With autoimmunity diseases, if you skip this tolerance phase, inflammation develops. The skin, for example, closely interacts with nerves and both produce substances that act on each other’s receptors. For example, neuropeptides can alter immune cells in the skin that produce cytokines and trigger an inflammatory response.

Can you talk about some of the environmental factors that researchers have found?

Most of the research that has been done is around environmental toxins that come from smoke or air pollution in large cities. Those toxins break up into small molecules, and certain immune cells have receptors for those small molecules. That triggers the activity of these immune cells, which release cytokines that induce inflammation wherever they are. Nutrition is also key - some foods induce inflammation, while other healthy foods don’t.

Why does the autoimmune response happen in some people versus others?

There are a lot of risk factors. One is genetics. You can have a genetic mutation that triggers a response. You could also have hidden mutations or hidden factors that are normally silent—you don’t realize that there’s this constant battle of anti-or pro-inflammation inside you, because it’s hidden. But then something happens, like an environmental trigger, such as a hydrocarbon—the chief component of oil and natural gas, for example—that activates receptors that your immune cells express. Then they will become pro-inflammatory, and then you have autoimmunity. Another trigger involves the microbiota—the microorganisms in our intestines. Your gut is the reservoir for immune cells—you have tons of bacteria in your gut and your immune cells live with them. They’re the so-called good bacteria. But then you eat something that somehow disrupts that, and all of a sudden, your immune cells start recognizing the bacteria as foreign. That happens, for instance, in Crohn’s disease and ulcerative colitis, though those diseases aren’t exclusively triggered that way.

Is the incidence of autoimmune disease increasing? And if so, is it because people are recognizing it more, or is it because there is more overall?

That’s a tough one. Autoimmune diseases have always been diagnosed, but maybe now there’s more diagnosis—perhaps because more people go more often to the doctor. But it’s clear that lifestyles have changed—working hard, not taking time for yourself, more stress, unhealthy fast food, more pollution—that definitely doesn’t help. And the environment is presenting more triggers. “It’s critical to learn as much as we can about the immune system, how it works in normal conditions, and how it reacts to different insults, so we can investigate how to modulate it, dampening or enhancing its response when needed to treat autoimmunity” says Dr.Alcaide.

This article was written by Taylor MacNeil and originally appeared in Tufts Now.

Read the original article about autoimmune disease