“CRP, ESR, FCP, oh my!” There’s nothing like a bowl of three-letter alphabet soup to make it feel like we’re not in Kansas anymore. If you’ve been diagnosed with IBD, then you are no stranger to the range of lab work and tests physicians use to monitor IBD and its side effects. Lucky for you, we at IBDCoach are here to give you the yellow brick road and ruby slippers to heel-click your way through this foreign terrain and make it feel more like home.

Why labs, tests, & scans are important for people with IBD

For many people with IBD, the severity of their disease is quite noticeable through the physiological symptoms they experience. From cramping to nausea and diarrhea, the body indicates its distress through a range of discomforts. That being said, sometimes a person’s day to day experience of IBD can be relatively uneventful (as in “clinical remission”), but lab work shows high levels of inflammation (not yet in “endoscopic remission”). Additionally, we know living with IBD can put a person at greater risk for other comorbidities and side effects.

A variety of tests are used to diagnose and monitor IBD directly, including X-rays, CT scans, white blood cell counts, endoscopy, and endoscopic ultrasounds. Other tests you may encounter are used to monitor those comorbidities and side effects like tests that check liver function, electrolytes or vitamin B-12 status, bone density, and even vision.

In this blog, we will focus on describing the measurable characteristics used to monitor inflammation in IBD, called biomarkers. Since each biomarker measures a slightly different aspect and specificity of inflammation, we believe it’s important for people with IBD to better understand the distinction between the most common inflammation indicators.

What do all these inflammatory biomarkers mean, anyway?

The four most common inflammatory markers measured for people with IBD include C-reactive protein, Erythrocyte Sedimentation Rate, fecal calprotectin, and fecal lactoferrin. The first two, C-reactive protein and Erythrocyte Sedimentation Rate, are found in the blood and are used to detect systemic inflammation. 

C-reactive protein (CRP) is an acute-phase reactant protein released from the liver in response to general inflammation. This can include infection, tissue injury, and especially the inflammation found during an IBD flare. Due to its role in generalized inflammation response, it is considered a nonspecific inflammatory marker. CRP is used clinically to detect IBD, monitor progress, and predict a patient’s response to biological therapies. This biomarker is considered to have moderate sensitivity and specificity. In other words, some people may not have a high CRP value, even though they do in fact have active inflammation. CRP is additionally useful to differentiate between IBD and IBS, but cannot give an indication of the degree of healing of the intestinal barrier. 

Similar to CRP, Erythrocyte Sedimentation Rate (ESR) is a nonspecific inflammatory marker as high levels are associated with not only inflammation, but also anemia, pregnancy, and even aging. It is used to both diagnose and monitor inflammation. Also similar to CRP, ESR is considered to have moderate sensitivity and specificity and so a normal result does not always equate to a lack of inflammation. Lastly, it has been reported that ESR does not respond as quickly as CRP. This means it may take more time to see a change in your ESR than the CRP value to accurately represent your disease activity.  

The other two commonly used markers of inflammation–fecal calprotectin and fecal lactoferrin–are detected by stool tests and are therefore much more specific to inflammation in the GI tract. 

Fecal calprotectin (FCP) is a protein found in neutrophils, a white blood cell that accumulates in the GI tract during active inflammation. Unlike the serum markers mentioned above, FCP is a very sensitive marker as it changes rapidly depending on intestinal inflammation. It is used for diagnosing IBD, monitoring disease activity, treatment guidance, and prediction of disease relapse. Similar to CRP, it can also be used to differentiate between IBD and IBS. A FCP at 50mg/L has been shown to predict relapse in patients with IBD with a sensitivity and specificity of 90% and 83%, respectively.1 

Fecal lactoferrin is an iron-binding protein found in neutrophils and so it is also used to assess elevated levels of neutrophil infiltration in the intestinal lumen. Clinically, fecal lactoferrin can help diagnose IBD, differentiate between IBD & IBS, and monitor disease activity. Lactoferrin is not as sensitive of an inflammatory marker as FCP. 

The limitations and the future

As for the future of IBD tests and biomarkers, there is plenty of work being done to advance our current technology! The IBD Biomarker Summit, hosted by the Crohn’s and Colitis Foundation, exists to identify and prioritize critical unmet needs in both clinical practice and research trials. One exciting advancement covered at their recent meeting was PGE-MUM, a new urine test for UC now in development in Japan. It targets a urinary metabolite associated with mucosal healing. To learn more about the progress covered at this summit, check out this Crohn’s and Colitis Foundation blog post

Furthermore, scientists at Vanderbilt University Medical Center, recently reported in Gastroenterology that a selenium transport protein produced in the colon may be a novel biomarker for patients with IBD.2 This is because selenium, which can act as an antioxidant in the colon, is one of the nutrients with reduced absorption in people with IBD. These exciting new findings give hope for finding more specific biomarkers that are tissue-specific. 

Overall, professionals seem to agree that although many of the existing tests and resulting biomarkers are powerful tools, they can be limited in scope. It is always important to speak with your doctor about each of your test results and advocate for more routine check-ups if you feel inclined to monitor your disease activity and treatment plan more closely. Because our current tests are not personalized and may not always be a perfect representation of your current disease state, it’s always important to listen to your gut and how you feel to know when things are off!

References 

1. Cappello, M. & Morreale, G. C. The Role of Laboratory Tests in Crohn’s Disease. Clin. Med. Insights Gastroenterol. 9, 51–62 (2016).

2. MacMillan, L. Potential biomarker for IBD severity, cancer risk identified. Vanderbilt University https://news.vumc.org/2021/02/04/biomarker-ibd-severity-cancer-risk/.

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