Calprotectin

Calprotectin

We have had many conversations around the role of faecal calprotectin clinically. We took this an opportunity to look into the matter to help better elucidate its use.

What is calprotectin?

Calprotectin is a calcium and zinc binding protein, which makes up around 60% of the cytosolic protein present inside granulocytes. The amount of calprotectin in faeces is therefore proportional to the amount of neutrophil migration from the inflamed bowel wall to the mucosa¹. In in other words, it tells you how active white blood cells are at the mucosal wall, which reflects how inflamed the gut wall is.

How is it measured?

It is generally measured through ELISA testing. The methodology can vary slightly, so it is always best to use the reference range that the lab provides when reading the results.

Why is it useful?

The gold standard for diagnosing inflammatory bowel disease (IBD) is a colonoscopy and biopsy. This is both an invasive and expensive procedure, and symptoms of IBD can mimic infection, irritable bowel syndrome (IBS) or other differential diseases. Calprotectin, when combined with symptoms, can be a useful screening marker to help to trigger further investigations.

From a functional medicine perspective, calprotectin can give clinicians an idea of the amounts of inflammation at the gut wall, which even in the lower ranges, may be a mediating factor in a systems approach to chronic disease.

What is the upper limit in the reference ranges?

Calprotectin has been adopted by the NHS in the UK, and many other healthcare professionals, to help screen between IBS and IBD without having to use a colonoscopy in the first instance. As it is a relatively new marker, the more it is used, the more information we have about the cut-off ranges and what levels are best to trigger investigation. Currently the NHS cut-off values vary slightly between each trust, as they often use different laboratories with slightly varying methodologies. NICE is recommending further research until a universal national cut-off can be agreed upon². This means some trusts are using a cut-off around 150 ug/g to trigger a referral, whilst other trusts are using closer to 250 ug/g.

Variability and lack of specificity

Faecal calprotectin is not specific for IBD alone. It can also be increased in the stool in other gut pathologies such as infectious enteritis, colorectal cancer, polyps, diverticulitis, food allergies and in patients using non-steroidal anti-inflammatory drugs³. Its use is not recommended to identify these diagnoses. Levels of calprotectin can fluctuate over a day in individuals.

How to use calprotectin in clinical practice

It is often best to think about calprotectin on a spectrum, and to use it in conjunction with the clinical presentation of your patient.

It is not diagnostic, as it is not specific enough. But it can be a great tool to help either: a) trigger further investigations; b) support your hypothesis of what may be happening at the gut wall; or c) as a monitoring tool in response to therapeutic interventions.

If you have a client with symptoms, and their calprotectin is under 50 ug/g, then it is unlikely something too sinister is going on.

If you have a client that presents with mid-range calprotectin (50-175 ug/g), then we should start thinking about what might be causing low level inflammation in the gut wall of this individual. Questions you might want to ask:

• Is there previous or known IBD?
• Is there previous or known diverticulitis or polyps?
• Is there any sign of acute enteritis or bacterial infection? i.e. Is the secretory IgA (SIgA) raised in the stool test, and is there a potential pathogen present in high levels?
• Is the client currently taking NSAIDS, proton pump inhibitors or drinking high levels of alcohol?
• Is there any blood in the stool test that might alert you to further gut damage?
• Is there mucous in the stool?

What to do if your client gets a high result of calprotectin

If your client has a high result of faecal calprotectin, has gastrointestinal distress symptoms and no current diagnosis of IBD, we recommend retesting the calprotectin through their General Medical Practitioner (GP) within 4-6 weeks. The GP will then trigger a referral to a gastroenterologist for further investigation if a repeat calprotectin comes back high.

You may wish to re-test mid-range levels of calprotectin as a useful monitoring tool in response to your intervention, or if your client as known IBD, it can also be a useful monitoring tool.