No difference in serum levels of B-cell activating receptor and antibodies against cytolethal distending toxin B and flagellin in post-infectious irritable bowel syndrome and chronic fatigue syndrome after <i>Giardia</i> infection.

Evidence Atlas

No difference in serum levels of B-cell activating receptor and antibodies against cytolethal distending toxin B and flagellin in post-infectious irritable bowel syndrome and chronic fatigue syndrome after Giardia infection.

Hanevik, Kurt, Saghaug, Christina, Aaland, Maren et al. · JGH open : an open access journal of gastroenterology and hepatology · 2022 · DOI

Quick Summary

This study looked for three potential biological markers (BAFF, anti-CdtB, and anti-flagellin antibodies) in the blood of people who developed ME/CFS and/or IBS after a Giardia infection. Researchers compared these markers in patients to healthy controls but found no significant differences between the groups. The findings suggest these three markers are not useful for diagnosing ME/CFS or IBS.

Why It Matters

Understanding potential biomarkers for ME/CFS is crucial for developing objective diagnostic criteria and understanding disease mechanisms, particularly in post-infectious presentations. This study's negative findings help clarify that previously proposed biomarkers may not universally distinguish ME/CFS patients, redirecting research toward alternative pathophysiological mechanisms.

Observed Findings

No significant difference in circulating BAFF levels between post-infectious fatigue/FGID patients and healthy controls
No significant difference in anti-CdtB antibody levels between patient groups and controls
No significant difference in anti-flagellin antibody levels between patient groups and controls

Inferred Conclusions

BAFF, anti-CdtB, and anti-flagellin antibodies cannot be considered universal biomarkers for distinguishing ME/CFS or IBS
Post-Giardia fatigue and gastrointestinal syndromes may not share the same immunological mechanisms involving these three markers as previously hypothesized

Remaining Questions

Do these biomarkers correlate with symptom severity or disease duration, even if not universally elevated?
Are there patient subgroups (e.g., specific IBS subtypes) in which these markers are elevated?
What alternative immunological pathways may underlie post-infectious ME/CFS and IBS?
Why do ME/CFS and FGID frequently co-occur if not through these proposed shared mechanisms?

What This Study Does Not Prove

This study does not prove these markers play no role in ME/CFS pathology—only that they are not universal distinguishing features between patients and healthy controls. The cross-sectional design cannot establish whether these markers preceded disease onset or result from it. Absence of difference in a single cohort does not exclude subgroup-specific associations.

Metadata

DOI: 10.1002/jgh3.12724
PMID: 35355666
Review status: Editor reviewed
Evidence level: Single-study or moderate support from human research
Last updated: 12 April 2026

About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →