Immune Expression in Children With Vesicoureteral Reflux: A Pilot Study
Related Experiment Video
Updated: Dec 6, 2025

An Immature Murine Model of Reversible Unilateral Ureteral Obstruction
Published on: April 4, 2025
Ashley W Johnston1, Jonathan C Routh1, J Todd Purves1
1Division of Urologic Surgery, Department of Surgery, Duke University School of Medicine, Durham, NC.
Insights
This pilot study found that children with vesicoureteral reflux (VUR) and bladder-bowel dysfunction (BBD) have increased immune cells in their bladder tissue. Pelvic inflammation may be a target for treating VUR and BBD.
Area of Science:
- Pediatric Urology
- Immunology
- Inflammation Research
Background:
- Vesicoureteral reflux (VUR) and bladder-bowel dysfunction (BBD) are common conditions in children.
- The local and systemic immune environment in VUR and BBD is not well understood.
Purpose of the Study:
- To explore the immune environment in children with VUR, with and without BBD.
- To identify potential immune-related therapeutic targets for VUR and BBD.
Main Methods:
- Pilot study of 7 children undergoing VUR surgery.
- Analysis of blood and bladder tissue using flow cytometry and LegendPlex assays.
- Assessment of immune cell composition, activation, and cytokine/chemokine levels.
Main Results:
- Increased immune cell infiltrates, including B cells and T cells, were found in the bladder tissue of patients with VUR and BBD compared to VUR alone.
- Elevated PD1 expression on T cells and PDL-1 on neutrophils was observed in VUR/BBD patients.
- Circulating immune cell percentages were similar between groups, but local bladder inflammation was higher in VUR/BBD.
Conclusions:
- VUR is associated with an immune-rich microenvironment, particularly when BBD is present.
- Pelvic inflammation severity correlates with BBD, suggesting it as a potential therapeutic target.
- Further research is warranted to investigate novel therapies targeting inflammation in VUR and BBD.
Objective:
To perform an exploratory, descriptive pilot study of the systemic and local immune environment in patients with vesicoureteral reflux (VUR) and bladder-bowel dysfunction (BBD).
Methods:
Consecutive children with VUR undergoing intravesical ureteral reimplantation were enrolled. Patients were assessed for presence of BBD by reported patient history and validated questionnaire. Fresh blood and bladder tissue, collected at the time of surgery, were immediately processed for analysis. Immune cell compositions were determined via flow cytometry. Immune cell activation was also defined at the time of analysis. LegendPlex assay analysis was utilized to define levels of circulating chemokines and cytokines.
Results:
A total of 7 patients were enrolled. Although percentages of circulating immune cells in the blood of those with VUR/BBD and VUR alone were similar, within bladder tissue, VUR/BBD demonstrated increased immune infiltrates compared to VUR alone. Bladder sample analysis showed that B cells, and Effector Memory and Naïve T cell percentages were significantly increased in VUR/BBD patients compared to VUR patients. T cell expression of PD1 was increased in bladder tissues of BBD/VUR. Additionally, analysis of circulating neutrophils displayed significantly increased upregulation of PDL-1 in patients with VUR/BBD vs those with VUR only.
Conclusion:
These pilot data suggest an immune-rich microenvironment is present within VUR. Severity of inflammation appeared to correlate with presence of BBD. This implies that targeting pelvic inflammation may be a novel therapy for children with VUR- or non-VUR-related BBD. Follow-up studies are currently underway.
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