Post-Infectious IBS and Calprotectin Elevation
Post-infectious IBS can have mildly elevated calprotectin levels, but these elevations are typically low-grade (generally <60 μg/g) and significantly lower than levels seen in inflammatory bowel disease.
Evidence for Calprotectin Elevation in PI-IBS
The Rome Foundation Working Team report on post-infection IBS specifically notes that PI-IBS patients have reduced numbers of calprotectin-positive macrophages compared to healthy subjects, indicating altered innate immune responses rather than active neutrophilic inflammation 1. This is a critical distinction from IBD, where calprotectin (a neutrophil-derived protein) is markedly elevated.
A cross-sectional study directly comparing PI-IBS to non-PI-IBS found that:
- 33% of PI-IBS patients had mildly positive calprotectin tests (T1 level: <15 μg/g) 2
- Only 9.8% of non-PI-IBS patients had similar mild elevations 2
- Importantly, none of the IBS patients (PI or non-PI) had moderate (15-60 μg/g) or high (>60 μg/g) calprotectin levels 2
- In contrast, 80% of IBD patients had T3 levels (>60 μg/g) 2
Clinical Interpretation Framework
When evaluating calprotectin in suspected PI-IBS:
- Levels <60 μg/g are consistent with PI-IBS, particularly if there's a clear history of preceding gastroenteritis 2
- Levels 100-250 μg/g warrant repeat testing or gastroenterology referral to exclude occult IBD, as this exceeds typical PI-IBS ranges 1, 3
- Levels >250 μg/g strongly suggest active IBD rather than PI-IBS and require urgent gastroenterology referral with endoscopic evaluation 1, 3
The British Society of Gastroenterology guidelines emphasize that calprotectin has excellent negative predictive value for excluding IBD, with levels <100 μg/g making IBS (including PI-IBS) the likely diagnosis 1, 4.
Pathophysiological Context
PI-IBS involves low-grade immune activation rather than active neutrophilic inflammation 1. The immune changes include:
- Increased mast cells and T lymphocytes in the lamina propria 1
- Altered cytokine profiles (elevated IL-1β, decreased IL-10) 1
- Increased intestinal permeability that persists after the acute infection resolves 1
These changes explain why calprotectin (primarily a neutrophil marker) remains relatively low in PI-IBS despite ongoing immune dysregulation 1.
Important Clinical Caveats
Before attributing elevated calprotectin to PI-IBS, exclude:
- NSAID use within the past 6 weeks, which can significantly elevate levels through direct mucosal injury 1, 3, 5
- Untreated celiac disease, which causes intestinal inflammation 3
- Colorectal neoplasia, particularly in patients over 50 or with alarm symptoms 3
- Active infectious gastroenteritis, which can markedly elevate calprotectin 5, 6
Ensure proper specimen collection: use the first morning stool and analyze within 3 days at room temperature to avoid falsely elevated results 1, 3, 5.
Practical Algorithm
For patients with suspected PI-IBS and elevated calprotectin:
- Calprotectin <60 μg/g: Consistent with PI-IBS diagnosis; treat as IBS in primary care 2
- Calprotectin 60-100 μg/g: Consider repeat testing after excluding NSAIDs and ensuring proper collection technique 1, 3
- Calprotectin 100-250 μg/g: Repeat testing or routine gastroenterology referral; this exceeds typical PI-IBS range 1, 2
- Calprotectin >250 μg/g: Urgent gastroenterology referral for colonoscopy; strongly suggests IBD rather than PI-IBS 1, 3, 2