Spondyloarthritis’s link to the gut: biomarkers

This week’s research is brought to you by my inability to leave anything that can be researched alone. I recently had a blood test report that there’s a good chance I have ulcerative colitis (UC), a type of inflammatory bowel disease (IBD). Constant back and forth with doctors leaves me worried that this will end up being nothing, yet hoping that it will be something. Especially since I’ve already mentally accepted that it could (probably) be something.

Countless times in the past I’ve had doctors get excited because a test seemed to show something. Inflammation! A positive blood marker! A little something here on this x-ray! And then they run more tests, it turns out to be nothing, and they get discouraged and lose interest. It’s so ubiquitous with spondyloarthritis, though, because there are no good tests for it.

It’s happened with my GI problems, too. I had an upper endoscopy many years ago that showed inflammation in my duodenum and blunting of my villi, but the doctor didn’t want to do anything but treat me for acid reflux. Since they couldn’t be explained, the atrophied villi weren’t brought up again. The follow-up to this blood test could actually bring answers after so many years, and I’m terrified it won’t.

In the course of investigating what blood tests for IBD can tell you, I’ve learned a lot about the antibody tests for IBD and their relationship to other autoimmune diseases, especially spondyloarthritis. It’s been hypothesized that autoimmune diseases are caused by problems in the gut (“leaky gut“), and there’s a lot of evidence for that with spondyloarthritis.

(See the bottom of the article for a glossary.)

What does an antibody test for IBD check?

My rheumatologist ordered a blood test that checks antibody levels for IBD. My blood test was positive for pANCA, an antibody to a type of white blood cell. It was negative for ASCA, an antibody to a yeast in the gut. This pattern is usually seen in ulcerative colitis patients. (The opposite test result, negative pANCA and positive ASCA, predicts Crohn’s disease.)

The test is cited as being anywhere from 90 to 98 percent specific for ulcerative colitis, and it’s also able to distinguish IBD from non-IBD causes of GI complaints. It’s especially used to determine if a patient has ulcerative colitis or Crohn’s disease. My results reported a 91% positive predictive value, meaning that since I got a positive test result, I have a 91% chance of having UC.

That’s still a 9% chance I don’t have UC. So what else could a positive result mean?

What does a positive pANCA test mean?

A positive pANCA test is not normal, even if it doesn’t necessarily mean a person has ulcerative colitis. Antibodies to your own white blood cells are not normal. Positive pANCA is used to diagnose other conditions, such as vasculitis, and the test can also be positive in people with lupus, rheumatoid arthritis (RA), and other autoimmune conditions.

Finally, finally, finally, I have an indisputable blood test that says something is wrong with me. Then I wondered: if pANCA can be positive in RA, what about spondyloarthritis?

IBD biomarkers and spondyloarthritis

The link between spondyloarthritis and IBD is significant. Researchers cite that 10 to 20 percent of people with IBD develop arthritis, and 5 to 10 percent of people with ankylosing spondylitis (a type of spondyloarthritis) develop IBD. In fact, many people with ankylosing spondylitis, even those without GI symptoms, have microscopic tears in the gut. There’s also a specific type of spondylitis associated with IBD, sometimes called enteropathic arthritis.

This has led researchers to investigate blood markers of IBD in patients with spondyloarthritis, including the antibodies pANCA and ASCA. These antibodies have both been found in patients with spondyloarthritis without IBD at much higher rates than the general population.

In fact, rates of ASCA are so high in patients with spondyloarthritis that ASCA is not very good at predicting Crohn’s disease in these patients. Interestingly, pANCA can still be used as an indicator of ulcerative colitis, because the rate of pANCA in people who have spondyloarthritis with UC is higher than the rate of pANCA in spondyloarthritis alone.

These antibodies being present in patients with ankylosing spondylitis proves that there is dysregulation of the mucosa in the intestine in patients with spondylitis, even those without IBD. Inflammation in the gut could play a significant role in how people develop spondylitis. Also, the link between ankylosing spondylitis and ASCA but not pANCA sheds some light on the fact that GI problems from ankylosing spondylitis are more like Crohn’s disease than ulcerative colitis.

There are many researchers who think that autoimmune diseases will one day all be linked to the gut, and spondyloarthritis seems like a good first target. I’m sure I’ll be writing more about autoimmunity and the gut soon!

-Bri

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Glossary of important terms:

• ASCA: Anti-Saccharomyces cerevisiae antibodies. S. cerevisiae is a yeast common in the gut.
• Biomarker: Something that can be measured in the blood to determine disease state.
• Crohn’s disease (CD): An autoimmune disease that causes inflammation throughout the digestive tract.
• Inflammatory bowel disease (IBD): Autoimmune diseases that cause inflammation of the digestive tract.
• pANCA: Antineutrophil cytoplasmic antibodies. Neutrophils are a type of white blood cell.
• Spondyloartharthritis or spondylitis (SpA): A group of inflammatory arthritides that attack the spine and large joints. Ankylosing spondylitis is a type of spondyloarthritis.
• Ulcerative colitis (UC): An autoimmune disease that causes inflammation in the colon (large intestine).