Can transferrin in stool samples indicate Inflammatory Bowel Disease (IBD)?

Transferrin in Stool Samples for IBD Diagnosis

Fecal transferrin is not a recommended biomarker for diagnosing inflammatory bowel disease (IBD), as current guidelines primarily recommend fecal calprotectin and fecal lactoferrin as the preferred stool biomarkers for IBD detection and monitoring.

Recommended Stool Biomarkers for IBD

Fecal Calprotectin

• Primary recommended biomarker: Fecal calprotectin is the most extensively validated stool biomarker for IBD diagnosis and monitoring 1, 2
• Diagnostic accuracy:
  • Sensitivity of 93% and specificity of 96% for diagnosing IBD in adults 1
  • Sensitivity of 92% and specificity of 76% in children and teenagers 1
• Interpretation thresholds:
  • Normal: <50 μg/g
  • Borderline: 50-150 μg/g
  • Elevated: >150 μg/g (indicates ongoing intestinal inflammation)
  • Highly elevated: >250 μg/g 2

Fecal Lactoferrin

• Secondary recommended biomarker: Fecal lactoferrin is another validated marker for IBD 1, 2
• Diagnostic value: Helps differentiate IBD from irritable bowel syndrome (IBS) or functional disease 1
• Threshold: 7.25 μg/g with 83% sensitivity and 75% specificity 2

Transferrin in IBD: Current Evidence

While transferrin is not recommended as a stool biomarker for IBD diagnosis, serum transferrin has been studied in relation to IBD:

1. Serum transferrin levels in IBD:

   • Reduced serum transferrin levels are observed in active IBD (both Crohn's disease and ulcerative colitis) 3
   • Transferrin negatively correlates with disease activity scores (CD: ρ = -0.49; UC: ρ = -0.52) 3

2. Diagnostic limitations:

   • Transferrin levels are affected by multiple factors including inflammation, malnutrition, anemia, and oxidative stress 3, 4
   • Recent research shows no significant differences in median transferrin concentrations between IBD patients and healthy subjects 4

3. Role in iron deficiency assessment:

   • Transferrin saturation (TfS) is used alongside ferritin to diagnose iron deficiency in IBD 1
   • In ulcerative colitis, TfS <16% (with normal CRP) or <11% (with elevated CRP) indicates iron deficiency 5
   • In Crohn's disease, transferrin-related markers have poorer diagnostic performance 5, 6

Recommended Diagnostic Approach for IBD

Initial Laboratory Testing

1. Inflammatory markers:

   • C-reactive protein (CRP)
   • Erythrocyte sedimentation rate (ESR) 1

2. Complete blood count:

   • Hemoglobin (anemia assessment)
   • Leukocyte count
   • Platelet count 1

3. Biochemical tests:

   • Serum electrolytes
   • Liver enzymes
   • Serum albumin (nutritional status assessment)
   • Renal function 1

4. Stool tests:

   • Fecal calprotectin (primary biomarker)
   • Fecal lactoferrin (secondary biomarker)
   • Rule out infectious causes (especially Clostridioides difficile and Cytomegalovirus) 1, 2

Definitive Diagnosis

• Endoscopy with biopsy: Remains the gold standard for IBD diagnosis 1, 2
  • Ileocolonoscopy examining the terminal ileum and all colonic segments
  • Precise description of lesions
  • Biopsies from affected and non-affected areas 1

Clinical Implications

1. Monitoring disease activity: Serial monitoring of fecal calprotectin levels at 3-6 month intervals is recommended for confirmed IBD 2

2. Predicting relapse: Elevated calprotectin in patients with quiescent IBD can predict clinical relapse with >85% sensitivity and specificity 2

3. Treatment guidance: Normalization of calprotectin should be a treatment goal in IBD management 2

In conclusion, while serum transferrin levels may be reduced in active IBD, fecal transferrin is not currently recommended as a diagnostic marker for IBD. Clinicians should rely on established biomarkers such as fecal calprotectin and lactoferrin, along with endoscopic evaluation, for accurate IBD diagnosis and monitoring.