A shared B-cell clonotype in patients with Interstitial Cystitis/Bladder Pain Syndrome presenting with Hunner lesions

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is characterized by bladder pain and lower urinary tract symptoms without obvious causes. A subset of patients with IC/BPS present with Hunner lesions (HL), which are focal regions of gross inflammation on the bladder wall. It has been previously proposed that cell populations within HL are enriched in B- and T-cells, suggesting that this form of IC/BPS may be caused by reaction to a specific antigen within the lesions. Alternatively, B-cell enrichment in the HL might be caused by generalized inflammatory processes. Here, we distinguished between these hypotheses by using single-cell sequencing to identify B-cell clonotypes in the HL and the bladder of IC/BPS patients. We identified a clonotype that is shared in two patients with IC/BPS and that represented a significant subpopulation of total immune cells within the lesions. This finding is strong evidence that B-cells in the patients’ bladders are reacting to a specific antigen. Further studies of this specific B-cell clonotype can identify the antigen, helping to define the pathophysiology for IC/BPS with HL.