Is Crohn’s Disease an Autoimmune Disease?

The understanding of how Crohn's disease is classified is changing

3D rendered Illustration of anatomically correct Monocyte immune system defense cells
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Crohn's disease is one form of inflammatory bowel disease (IBD). It primarily affects the digestive system, causing inflammation. Ulcers and inflammation from Crohn's disease can occur anywhere in the digestive system and affect other parts of the body, including the skin, joints, and eyes.

As more research is completed, understanding what causes IBD will improve, leading to better treatments and individualized medicine.

Scientists do not know what causes Crohn's disease, but it does appear to be hereditary with an environmental trigger. There has been some research that tries to understand how to classify Crohn's disease.

However, the disease does not cause the creation of antibodies. For that reason, it's not accurate to call Crohn's disease an "autoimmune" condition. The researchers who study IBD are now shifting to referring to it as an immune-mediated condition or an autoinflammatory condition.

What Is an Autoimmune Disease?

The immune system is an important part of the body's defense system. It can minimize or prevent infections and diseases caused by all sorts of foreign invaders and substances. The adaptive (acquired) immune system learns what a virus, bacteria, parasite, or fungus is and how to attack it.

When the immune system works well, most people don't notice that it's there or doing its job because the main function is to prevent illnesses.

However, things can go wrong with the immune system. There are several theories about how autoimmune conditions develop. One of the main ideas is that an event spurs the adaptive immune system to spring into action—such as an infection from a virus, for example.

The adaptive immune system develops and learns over time to target specific things that invade the body and cause disease. Sometimes it can erroneously see the body's own cells as invaders and attack them. Healthy tissue suddenly becomes the enemy, and this can wind up causing disease.

When the immune system goes haywire in this way, it can lead to a chain reaction that spurs the creation of antibodies against components of a person's cells rather than invaders. These are called autoantibodies.

The autoantibodies play a role in causing the inflammation associated with autoimmune diseases. This is why some autoimmune conditions are treated with medications that suppress parts of the immune system. Tests can identify specific antibodies, but not everyone who has autoantibodies will develop an autoimmune disease.

However, no antibody has been identified to be associated with Crohn's disease. No blood test can find the "Crohn's" antibody and diagnose the disease, as is the case for other autoimmune conditions.

There are more than 80 identified autoimmune diseases. They run the gamut from those that are more common, such as celiac disease and rheumatoid arthritis, to rare conditions such as Kawasaki disease and myasthenia gravis.

Many autoimmune disorders are chronic and require treatment throughout a person's lifetime. Some, however, can be self-limiting or might be treated effectively, so they don't require continuous management. Autoimmune conditions tend to affect women more often than they do men.

What Is an Autoinflammatory Disease?

A second part of the immune system is called the innate immune system. The innate immune system is something people are born with. It is controlled by genes inherited from a person's parents.

It is the body's first defense against an invasion by a harmful germ or other substance. It reacts quickly to deal with a foreign invader, causing symptoms such as fever, heat, and swelling. The innate immune system has evolved over millions of years.

Like any other type of gene, the genes that encode for the innate immune system can sometimes undergo changes. These changes can affect how the immune system reacts.

In some cases, this could mean that the innate immune system cannot tell the difference between healthy tissue that is part of the body and a substance that needs to be attacked. When the innate immune system mistakenly thinks that body cells are foreign invaders, it goes on the offensive and causes inflammation.

The inflammation caused by the innate immune system acting in this way can occur throughout the body, which is called a systemic response. This inflammatory response can become chronic, meaning that it goes on for a long time.

Crohn's and the Gut Microbiome 

Another factor to consider in the development of Crohn's disease is how all the microorganisms that live in the digestive system (called the microbiome) play a role. It's known that people with Crohn's disease do not have the same balance of healthy strains of bacteria in their gastrointestinal (GI) tracts as people who don't live with the disease.

One of the reasons it has been so difficult to understand the causes of IBD is that the microbiome is complex and not yet well understood. It's not a matter of one or even a few strains of bacteria being either too numerous or not numerous enough.

There are, however, trends seen in the microbiome shift in people who live with Crohn's disease. This helps get closer to understanding a cause and developing treatments, but it's clear that not every case of Crohn's disease affects the microbiome in the same way.

This ties into the immune response because it's also thought that in IBD the immune system might be mistakenly attacking normal bacteria in the gut. This has been described as a "breakdown in relations" between the bugs living in the gut and the immune system.

Over time, it's thought that chronic dysbiosis (which refers to a lack of balance in the microbiome) is one of the factors that lead to the development of Crohn's disease.

Genetics, Crohn's, and Autoinflammatory Disease 

It's now also known that Crohn's disease has a genetic piece. Hundreds of genes are connected to the various forms of IBD.

That makes Crohn's a condition that can be inherited, but not everyone with the genes will develop the disease. In fact, most people who live with Crohn's disease don't have a relative who has the disease.

Changes in the genetics of the innate immune system play a role in the development of Crohn's disease, but that's not the only piece of the puzzle. There is also an environmental trigger—something that causes the innate immune system to start the inflammatory process and not stop. It's thought that there could be many different triggers that contribute to IBD.

According to Marla Dubinsky, MD, director of the Pediatric Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center and associate professor of pediatrics at Cedars-Sinai Medical Center, "IBD actually fits into the category of autoinflammatory conditions, which is distinct from an autoimmune condition."

Dr. Dubinsky says that in Crohn's disease, "...the innate immune system becomes confused and causes inflammation without threats being present." Without that autoantibody piece, Crohn's disease can't be placed into the autoimmune disease category.

Crohn's disease affects the digestive tract, but other body systems are affected as well. This is another factor that points to it being a systemic innate immune system-related disorder. It is common for people with Crohn's disease to develop other conditions (such as arthritis) caused by an inflammatory response.

According to Dr. Dubinsky, "While a specific body system might be mainly affected, like the GI tract in Crohn’s disease, the nonspecific nature of the innate immune system means that other systems are inevitably affected as well." 

Other Diseases Associated With Crohn’s

People who live with Crohn's disease may also have other conditions, especially those considered immune-mediated (caused by a problem with the immune system). It's thought that some of the related conditions may have a similar inflammatory pathway as Crohn's disease.

The problem with the immune system that causes IBD may also trigger other immune-mediated conditions. The risk of developing another condition is dependent upon a host of factors, including the type of IBD (Crohn's disease or ulcerative colitis), age, sex, disease severity, and ethnicity.

Many studies involving people who live with an IBD include too few patients from Asian, African, and Latino backgrounds, leaving an open question about how these patients are/are not affected by related conditions. People who live with an IBD should consult their physicians on how to screen for related conditions.

Some of the more common inflammatory conditions that can occur in people who live with Crohn's disease include ankylosing spondylitis, pyoderma gangrenosum, psoriasis, iritis, episcleritis, and primary sclerosing cholangitis.

Triggers

The exact mechanism of the development of Crohn's disease is unknown, but it is thought to include several different factors. There is the genetic component, with hundreds of genes known to be associated with the disease.

Then there is an environmental trigger (or, likely, more than one) and/or a shift in the microbiome. Together, these things are thought to send the immune system into an inflammatory loop, attacking the digestive tract and other body systems.

Environmental triggers may include:

  • Air pollution
  • Appendectomy
  • Diet
  • Exposure to heavy metals
  • Living in an urban area
  • Medications
  • Physical activity level
  • Smoking (and secondhand smoke)
  • Stress
  • Sleep
  • Vitamin D levels

The extent to which one or more of these potential triggers is involved in a particular case of Crohn's disease is unknown. Further, there is a lack of understanding of how the microbiome interacts with the external triggers and eventually leads to the development of disease.

There is some research showing that people with IBD have a smaller number of different species in their microbiomes. It's thought that this lack of diversity may contribute to the development of some forms of Crohn's disease. 

Categorizing Crohn’s Disease

How to categorize Crohn's disease is an evolving conversation. In the past, it has been referred to as an autoimmune condition. But it is now understood that it is not autoimmune because it lacks the conditions that need to be met for that classification. Crohn's disease is more accurately described as autoinflammatory.

Some research discusses IBD as being the result of an immune deficiency. This theory points to a defect within the white cells of people who live with an IBD. However, that theory has also become less well accepted in recent years and may not encompass the spectrum of Crohn's disease.

It's known that the immune system has a role in the development of Crohn's disease. However, the understanding of how various factors interact in the development of the disease is far from complete.

It's also thought that Crohn's disease may actually encompass many different disorders. That could mean there are many different types of the disease as well as a spectrum of causes.

In some cases, Crohn's disease and IBD in general are also referred to as "immune-mediated" conditions. This is a broader term that encompasses all the conditions related to the dysregulation of the immune system. As more research is completed, the understanding of what causes IBD will improve, leading to better treatments and individualized medicine.

Summary

Crohn's disease is not an autoimmune disease because people with the condition don't have antibodies that target their own bodies. Research is ongoing to understand the causes of Crohn's disease and how it should be classified. There is a shift toward calling it an immune-mediated condition or an autoinflammatory condition.

A Word From Verywell

While there is still so much unknown about Crohn’s disease, research is starting to uncover what may cause it. The process doesn’t appear to be autoimmune in nature but rather an immune-mediated response.

It could be that the cause of Crohn’s disease is that the immune system is trying to respond to a threat, but there actually isn’t any threat present. This leads to inflammation that targets the digestive system but also can affect the rest of the body.

However, it is not an autoimmune response because antibodies are not found in Crohn’s disease. It may be more correct to call Crohn’s disease an immune-mediated disease or an autoinflammatory disease.

Frequently Asked Questions

Does Crohn’s disease affect the immune system?

It's understood that there is a connection between Crohn's disease and the immune system. A combination of factors—genes, an environmental trigger, and an inappropriate response from the immune system—are thought to work in concert in the development of the disease.

Which autoimmune diseases are associated with Crohn’s disease?

Some of the inflammatory and autoimmune conditions that are most often found in people who live with IBD include:

What causes Crohn's disease?

Experts and researchers do not know what causes Crohn’s disease. It’s currently called an idiopathic disease, one for which the cause is not known or understood. The disease does tend to run in families, but most people with IBD do not have a close family member with the disease.

There have been hundreds of genes found that are associated with IBD. However, not everyone who has these genes will go on to develop a form of the disease.

The theory is that there are environmental triggers that “turn on” the disease. These could be any combination of things that affect the makeup of the bacteria, viruses, and fungi found in the digestive system (the gut microbiome). The factors that change the microbiome could include the environment, diet, and/or genetics.

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