APRIL/BAFF upregulation is associated with clonal B-cell expansion in Hunner-type interstitial cystitis.
Masafumi Horie1, Yoshiyuki Akiyama2,3, Hiroto Katoh4
1Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
The Journal of Pathology
|October 3, 2024
Summary
Hunner-type interstitial cystitis (HIC) involves significant plasma cell infiltration in the bladder. APRIL and BAFF proteins drive B-cell expansion, suggesting new therapeutic targets for this chronic condition.
Area of Science:
- Immunology
- Urology
- Pathology
Background:
- Hunner-type interstitial cystitis (HIC) is a chronic inflammatory bladder condition with unknown causes.
- Understanding the underlying immune mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the immunogenomic landscape of HIC-affected bladder tissue.
- To identify key cellular players and molecular pathways involved in HIC pathogenesis.
Main Methods:
- Comprehensive immunogenomic profiling of bladder biopsies and cystectomy specimens from 37 HIC patients.
- Next-generation RNA sequencing to analyze gene expression and cellular infiltration.
- B-cell receptor repertoire analysis to assess B-cell clonal expansion.
Main Results:
- Abundant plasma cell infiltration with light chain restriction was observed in HIC bladder tissue.
- Significant spatial and temporal expansion of B-cell clones was identified.
- B-cell clonal expansion strongly correlated with increased expression of TNFSF13 (APRIL) and TNFSF13B (BAFF).
Conclusions:
- APRIL and BAFF are key regulators of clonal B-cell expansion in HIC.
- These cytokines represent potential therapeutic targets for managing HIC.
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