What is calprotectin?

Calprotectin: A Key Biomarker for Intestinal Inflammation

Calprotectin is a calcium- and zinc-binding protein primarily derived from neutrophils that serves as a sensitive and specific marker of intestinal inflammation, making it an essential non-invasive diagnostic tool for differentiating inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS) in patients with chronic gastrointestinal symptoms. 1

What is Calprotectin?

• A 36kDa protein belonging to the S100 family of proteins 2
• Predominantly found in neutrophils' cytoplasm 3
• Has direct antimicrobial properties and plays a role in innate immune response 2
• Present in various body fluids, with fecal concentration approximately six times higher than plasma levels 2
• Released into the intestinal lumen during inflammatory processes when neutrophils migrate into gastrointestinal tissue 4

Clinical Utility of Fecal Calprotectin

Differentiating IBD from IBS

• Excellent negative predictive value for ruling out IBD in symptomatic patients 5
• Recommended as an initial screening test in primary care for patients with chronic diarrhea or lower GI symptoms persisting >4 weeks 1
• Normal levels (<50 μg/g stool) have high negative predictive value for IBD 5

Diagnostic Thresholds

• Cut-off values vary between assays, but generally:
  • <50 μg/g: Normal (low likelihood of IBD)
  • 50-100 μg/g: Borderline
  • 100-250 μg/g: Intermediate (consider referral to gastroenterology)

  • 250 μg/g: High (strongly suggests active inflammation, urgent referral recommended) 5, 1

Sensitivity and Specificity

• 50 μg/g cutoff: 90.6% sensitivity for detecting endoscopically active disease 5

• 100 μg/g cutoff: 78.2% specificity 5

• At cutoff 50-60 μg/g: 81% sensitivity and 87% specificity for organic disease 5

Clinical Applications

IBD Management

• Monitoring disease activity in known IBD patients 5
• Predicting disease relapse 1
• Assessing response to treatment 1
• Evaluating mucosal healing 3
• Alternative to invasive procedures like colonoscopy for assessing inflammation 5

When NOT to Use Fecal Calprotectin

• Acute diarrhea due to infection (calprotectin will be elevated regardless) 5
• Patients with bloody diarrhea (requires flexible sigmoidoscopy regardless) 5
• Suspected colorectal cancer (not sensitive enough for exclusion) 5
• Patients with rectal bleeding, change in bowel habit, weight loss, or iron-deficiency anemia (cancer pathway referral recommended) 5

Important Considerations

Confounding Factors

• NSAID use within past 6 weeks can falsely elevate levels 1
• Age can affect normal reference ranges 2
• Day-to-day variation in levels 2
• Elevated levels can persist for weeks after infectious gastroenteritis 1

Proper Sample Collection

• First morning stool sample preferred 1
• Sample stable for up to 3 days at room temperature 1

Clinical Decision Algorithm

1. For patients with chronic gastrointestinal symptoms without alarm features:

   • Measure fecal calprotectin after excluding infection and celiac disease

2. Interpret results:

   • <50 μg/g: IBD unlikely, consider IBS management
   • 50-100 μg/g: Consider repeat testing
   • 100-250 μg/g: Consider gastroenterology referral

   • 250 μg/g: Urgent gastroenterology referral recommended

3. For known IBD patients:

   • Use to monitor disease activity and treatment response
   • Rising levels may indicate relapse before clinical symptoms appear

4. For patients with alarm symptoms (rectal bleeding, weight loss, anemia):

   • Refer via suspected cancer pathway regardless of calprotectin level 5

Fecal calprotectin represents a significant advancement in non-invasive assessment of intestinal inflammation, allowing for better patient stratification, reduced unnecessary invasive procedures, and improved monitoring of disease activity in IBD patients.