Genetics only part of cause

Pilar Alcaide (Immunologist) - 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. 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.

Do scientists know why this autoimmune response happens?

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. 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.

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.

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.

What are 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.

Do the biologicals used in treatment for autoimmune disease have downsides?

Yes, they do. One is that, because of their immunosuppressive nature, sometimes when you take them for too long, some lymphomas form—cancer of the lymph nodes—because lymphoid tissue is where immune cells divide. They also have other side effects such as higher risk of infections.

The gold standard would be to find something that is more tissue specific, that you wouldn’t dampen inflammation systemically. But for some autoimmune diseases, you need to dampen it systemically as well.

Are autoimmune diseases more common in higher income countries vs. poorer countries?

It’s hard to tell, because a lot of people in poor countries are not diagnosed. Some autoimmune diseases are related to ethnicity. For instance, autoimmune skin disease like vitiligo and psoriasis are prevalent in the Middle East.

Are autoimmune diseases more difficult to diagnose than other diseases?

I think they’re difficult to diagnose because if it’s systemic, there are a lot of cross relations between that and other diseases.

And there are people who present with more than one autoimmune disease. There are just so many different autoimmune diseases—more than are probably realized.

That’s why 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.

Most of the diseases that kill the majority of the people are somehow immune-related, so understanding immunity will help prevent and treat not only autoimmunity but also other chronic inflammatory diseases.- Source: Newswise.com

Did you know?

Vitamin D

No single autoimmune disease was reliably prevented by vitamin D supplementation.

Health tip

Turmeric is especially beneficial for fighting inflammation

Health precaution tip

Green tea is a potent food for autoimmune diseases

See a doctor when

STATS

What causes autoimmune diseases?

• Some medications. ...

• Having relatives with autoimmune diseases. ...

• Smoking.

• Already having one autoimmune disease. ...

• Exposure to toxins.

• Being female — 78% of people who have an autoimmune disease are women.

• Obesity.

• Infections.