explanation of relationship to faecal calprotectin and bowel related inflammation

Last edited 02/2023 and last reviewed 02/2023

Explanation of relationship to calprotectin and bowel related inflammation

Faecal calprotectin is excreted in excess into the intestinal lumen during the inflammatory process and so can act as a marker for inflammatory diseases of the lower gastrointestinal tract. Tests measuring faecal calprotectin can help to distinguish between inflammatory bowel diseases and non-inflammatory bowel diseases (1).

  • Calprotectin is a 36-kDa calcium and zinc binding protein that accounts for about 60% of total proteins in the cytosol fraction in neutrophil granulocytes
    • calprotectin has an antimicrobial activity

    • calprotectin is probably involved in the regulation of inflammatory reactions

    • calprotectin is resistant both in vitro and in vivo to enzymatic degradation - levels of calprotectin can be easily measured in the stools

    • calprotectin accounts for 60% of the cytosolic protein in neutrophils, and, to a lesser extent, in monocytes and macrophages which can be found throughout the human body mainly in plasma, urine, cerebrospinal fluid, faeces, saliva or synovial fluid

    • involved in many physiological functions including cell differentiation, immune regulation, tumourigenesis, apoptosis and inflammation

    • accounts for approximately 60% of total soluble proteins in the cytosol fraction of neutrophils
      • neutrophils are the common effector cells that define acute inflammation in response to a number of factors
        • once the neutrophil migrates to a site of chemoattraction, the contact sets off a cascade of events leading to a respiratory burst, oxygen radical generation, and disintegration of the neutrophil with the release of its cytosolic granules (and calprotectin), which contain a variety of hydrolytic and proteolytic enzymes.
        • thus the neutrophil deals with the chemoattractant but at the same time causes indiscriminate damage to its surroundings

    • amount of calprotectin reflects the number of participating neutrophils in this inflammation
  • calprotectin is highly resistant to degradation by intestinal pancreatic secretions, intestinal proteases, and bacterial degradation and it is stable in feces at room temperature for at least a week. In short, the amount of calprotectin in feces provides a noninvasive quantitative measure of neutrophil flux to the intestine.

Sensitivity and Specificity in Inflammatory Bowel Disease (IBD)

  • analysis of faecal calprotectin consists of an extraction step followed by quantification by immunoassay
  • due to its specificity for gastrointestinal tract inflammation, faecal calprotectin is superior to serum calprotectin (3)
  • an abnormal test result simply indicates intestinal inflammation of any cause
    • numerous intestinal diseases and drugs (eg, NSAIDs, alcohol) associated with low-grade intestinal inflammation with average calprotectin levels between 50 and 300 mug/mg
    • however, only untreated IBD and certain food infections are associated with very high levels (2)
      • given a degree of clinical disease activity in, for example, Crohn's colitis and small bowel Crohn's disease, it is noteworthy that calprotectin is somewhat lower in the latter
        • due to that the small bowel bacterial load (the main neutrophil chemoattractant) is far less than in the colon and, hence, reflected by a less intense inflammatory response. This is also reflected by histology
    • nearly 99% of patients who have active IBD have elevated fecal calprotectin levels
      • 15% to 20% of patients with IBS have mildly elevated calprotectin levels. (It is important to note that patients with postinfectious or postdiverticulitis IBS-like symptoms may have been included in these studies, and these diseases differ from conventional IBS.)
      • a normal calprotectin level is much more likely to represent IBS (2)
    • additional utility of faecal calprotectin is that changes in its levels are a good indicator of mucosal healing or recurrence of inflammation (3)
      • faecal calprotectin can be used for monitoring of patients with IBD and to identify the patients at risk of relapse
    • FC has a false positive rate of up to 9% based on negative upper and lower gastrointestinal endoscopic findings in patients with elevated FC without taking into account the possibility of significant small bowel pathology (4)

Faecal calprotectin is a poor marker for differentiating colorectal carcinoma from adenoma (3)

  • not recommended as a screening marker for colorectal carcinoma in asymptomatic patients

A review notes (5):

  • Faecal calprotectin testing
    • is recommended in patients <60 years old with lower gastrointestinal symptoms and normal initial workup to exclude causes of colonic inflammation
    • a normal faecal calprotectin result has a high negative predictive value for inflammatory bowel disease, and prevents unnecessary investigation when the most likely diagnosis is irritable bowel syndrome
    • should not be used in patients older than 60 or if colorectal cancer is suspected
    • is a sensitive marker of intestinal inflammation and may be elevated in conditions other than inflammatory bowel disease, such as diverticulitis and infectious gastroenteritis, or when patients take medications such as non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin

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faecal calprotectin