Is Ulcerative Colitis an Autoimmune Disease?

Written by Stephanie Booth
Medically Reviewed by Melinda Ratini, MS, DO on April 30, 2025
9 min read

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD). It causes painful sores and inflammation deep inside your colon and rectum. That can lead to hard-to-manage symptoms like diarrhea, constipation, an urgent need to poop, and belly pain.

There’s no cure for UC, but doctors keep asking questions about this complex condition, including: Is ulcerative colitis an autoimmune disease?

Although there’s still more to be learned, most doctors believe the answer is yes. 

Your immune system is a complex network of organs, tissues, and cells that work together to protect you from threats like germs, viruses, and cancer-causing cells.

But sometimes, it can overreact and attack healthy parts of your body, causing what’s called an autoimmune disease.

Between 80 and 100 autoimmune diseases have been found. UC is one of the most common types. 

Some experts refer to UC as an immune-mediated inflammatory disease (IMID). That means that autoantibodies – special proteins made by your body’s immune system to attack its own cells – are not involved.

What’s the difference?

“As far as I'm concerned, it's just a matter of semantics,” says Babak Firoozi, MD, a gastroenterologist at MemorialCare Orange Coast Medical Center in Fountain Valley, CA. 

“As far as autoimmune diseases are concerned, you’ll have a series of blood tests and specific antibodies which are abnormal. That suggests specifically that your body's immune system is attacking something in your body that it's not supposed to be attacking,” Firoozi says. “There's not a specific antibody that we can test for ulcerative colitis. However, the disease process is the same. It's the immune system basically out of control and leading to inflammation and leading to tissue damage, to the point where we have to intervene with medications that suppress the immune system. And we use a lot of the same medications with ulcerative colitis that we use with other autoimmune diseases.”

Here are the different ways experts have learned UC is autoimmune.

Gene changes

In the past 20 years, researchers have found over 200 gene mutations that can increase your risk of IBD.

For instance, some genes help to keep the lining of your digestive tract strong and intact. That way, your gut bacteria and any toxins in your food can’t leak into the rest of your body. If this lining isn’t protected as well as it should be because of mutated genes, bacteria and toxins may seep through to other tissues. That could trigger an immune reaction.

Other genes linked to UC – like IL23R and HLA complex – help keep your immune system running smoothly. For instance, some help regulate your T cells. These are special “fighter” cells that protect your body against harmful germs and other threats. A mutated gene could let your T cells overreact. That could cause ongoing swelling, tenderness, and irritation in your colon.

Having a family member with UC makes it more likely that you’ll have it, too. But UC is a complex condition. It’s likely that many different factors play a role, not just the genes you were born with.

Loss of immune tolerance

Between 300 and 500 helpful types of bacteria naturally live in your gut. Your immune system should know that they’re not a risk to your health and can be safely ignored. But if your immune system isn’t working the way it should, it may try to attack your gut biome, leading to inflamed tissue and upsetting this delicate balance of bacteria. 

Chronic inflammation

Sometimes, UC appears to be triggered by a big reaction from your immune system. It could be an infection in your gut, like a virus that causes intense vomiting and diarrhea. Or it could be taking a medication like antibiotics, aspirin, and NSAIDs (nonsteroidal anti-inflammatory drugs). When any of these things irritate the lining of your digestive tract, your immune system responds. But it may keep responding, even after the threat has gone away.

Environmental factors

IBD, including UC, is becoming more common around the world. Experts believe that some things around us, which can affect our genes, may help explain why. Some environmental factors that have been linked to UC include:

  • Ultra-processed foods
  • Hormones in birth control
  • Tobacco use
  • Air pollution
  • Stress

Experts are still trying to figure out the links. Things around you could increase your risk of UC. Or they may upset the balance between helpful and harmful bacteria in your gut, which could lead to chronic inflammation.

While having an autoimmune issue can increase your risk of UC, the opposite is also true. Having UC can make you more likely to have another immune mediated inflammatory disease (IMID).

That’s because UC can cause inflammation to spread to other parts of your body. It can also weaken your immune system and throw your gut bacteria out of balance. That may raise your risk of conditions like: 

  • Asthma
  • Multiple sclerosis
  • Psoriasis
  • Rheumatoid arthritis
  • Vasculitis

Doctors have many different ways to figure out whether you have UC. A newer blood test can now check for autoimmune markers (antibodies) that your immune system makes. If you have UC, your blood sample could contain perinuclear anti-neutrophil antibodies (pANCA).

This test isn’t 100% accurate, though. Some people with UC don’t have any pANCA in their blood. Or another biomarker, anti-saccharomyces cerevisiae antibody (ASCA), could show up. ASCA is linked with another type of IBD called Crohn’s disease, but some people with UC have it, too. 

Experts are looking for other inflammatory markers that may be helpful. Among them are:

  • Calprotectin, a protein that’s found in your poop. It may predict when your UC is about to flare.
  • C-reactive protein (CRP) levels can help your doctor choose a UC treatment for you.

Doctors can use many types of medications to manage your symptoms and try to prevent them from coming back.

Immunosuppressants – also called immunomodulators – work by changing or weakening your immune system. For instance, they may reduce the number of immune cells your body makes or how well certain cells function. That can decrease inflammation, allow your gut tissue time to heal, and reduce your symptoms.

“Once we make the diagnosis of ulcerative colitis, you want to have a medication that gets your disease under control and in remission. And more often than not, these are with immunomodulatory therapies,” Firoozi says.

Immunosuppressive treatments for UC include:

Corticosteroids (including budesonide and  prednisone), which tamp down your entire immune system. “Unfortunately, [people with UC] have flares every once in a while, and the most common way that we manage them is with a short course of steroids,” Firoozi says.

Thiopurines kill T cells, which rev up inflammation. They also prevent some specific immune cells from working. The most common ones prescribed for IBD are:

  • 6-mercaptopurine (Purinethol, Purixan)
  • Azathioprine (Azasan, Imuran)

Methotrexate (Jylamvo, Trexall, Xatmep), which lowers inflammation in your body, keeping a specific protein from working.  

Calcineurin inhibitors (CNIs) target an enzyme called calcineurin that helps make T cells. These drugs aren’t common but could be given to you in the hospital.

  • Cyclosporine (Gengraf, Neoral, Sandimmune)
  • Tacrolimus (Astagraf XL, Envarsus XR, Prograf)

Biologics are antibodies that prevent proteins in your body from causing inflammation. They’ve been used to treat UC for over 20 years. 

Some examples include:

  • Adalimumab (Humira)
  • Golimumab (Simponi)
  • Guselkumab (Tremfya)
  • Infliximab (Remicade)
  • Mirikizumab-mrkz (Omvoh)
  • Risankizumab-rzaa (Skyrizi)
  • Ustekinumab (Stelara)
  • Vedolizumab (Entyvio)

Other targeted medicines

Sometimes called small molecule medicines, these are newer medications that work a lot like biologics but are less complex.

  • Etrasimod (Velsipity)
  • Filgotinib (Jyseleca)
  • Ozanimod (Zeposia)
  • Tofacitinib (Xeljanz)
  • Upadacitinib (Rinvoq)

Some of these treatments are taken by mouth or given to you in a shot. Others are put into your body through an IV.  

The treatment your doctor chooses for you will depend on many things.

Immunosuppressants can be helpful if you’re having a mild to moderate flare-up. Your doctor could also prescribe them at a time when you’re doing well. Taking this type of medicine could help keep your symptoms from coming back for a while.

Things to keep in mind when you’re using immunosuppressants for UC

Like all medications, immunosuppressants can cause side effects. These will depend on the type of drug, but could include:

  • Headache
  • Nausea
  • High blood pressure
  • Anemia (low red blood cells)
  • Tingling in your hands and feet
  • Mouth sores
  • Allergic reaction
  • Hair loss
  • Inflammation in your lungs, pancreas, or liver
  • Increased risk of infection
  • Small but increased long-term risk of some cancers

Because of this, your doctor will want to keep a close eye on you while you’re taking immunosuppressants. Make sure to complete any scheduled lab work and go to your regular doctor visits. 

If you notice signs of an infection, like a fever, let your doctor know right away. 

Some treatments for UC aren’t safe to take if you’re pregnant. Before you start any medication, tell your doctor if you think you may be pregnant or if you want to start a family.

Talk to your doctor about how to manage your symptoms when you’re in the midst of a flare. For instance, you could:

Eat smaller amounts of food throughout the day. That could be easier on your digestive system than three big meals.

Skip high-fiber foods for the short term. For instance, you may want to stay away from foods like nuts, seeds, and popcorn until your symptoms improve. Instead of salads and raw produce, grill, bake, or steam your vegetables. 

Watch what you drink. Avoid alcohol, caffeine, and carbonated drinks. Although more research needs to be done, dairy products may also worsen a flare-up. Instead, drink plenty of water.

Monitor your stress levels. Being aware that stress could cause your symptoms to flare is a good first step. Try getting regular exercise, since that can help boost your mood. You might also find that meditation or joining a support group helps. If you need more ways to deal with stress, talk to a counselor or therapist.

Get plenty of rest. Your immune system needs plenty of sleep to function well. Not getting enough can actually increase inflammation in your body and lower your tolerance to pain.

Quit tobacco. Smoking can worsen your symptoms and make them harder to treat. If you need help quitting, let your doctor know so they can help.

Let your doctor know right away if you have new or worse symptoms. It’s also important to tell them if you feel like your usual treatments aren’t working well.

Ulcerative colitis happens because of an issue with your immune system. The reason is likely complex, involving both genetic and environmental factors. There’s no cure, but different treatments can manage your symptoms and try to prevent them from coming back. Immunosuppressants, which slow down or change how your immune system works, are often prescribed. Working closely with your doctor is crucial, especially when you’re going through a flare.

Is ulcerative colitis immune-mediated?

Immune-mediated inflammatory diseases (IMIDs) are conditions that involve an excessive or “wrong” response from your immune system. That includes many different health issues, including ulcerative colitis, rheumatoid arthritis, type 1 diabetes, and asthma.

Does ulcerative colitis weaken the immune system?

When you have ulcerative colitis, your immune system overreacts. It attacks healthy tissue in your colon and rectum, which causes it to be sore and inflamed.

Treatment for ulcerative colitis involves getting your immune system under control. That can reduce inflammation and allow sore, swollen areas in your gut to heal. To do that, you may need to take medication that can suppress, or shut down, parts of your immune system.

Always talk to your doctor if you have questions about how to protect your health.