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

Tabansky, Inna; Moldwin, Robert; Liu, Min; Najjar, Souhel; Keskin, Derin B.; Nursey, Vishaan; Laurent, Micheline; Birder, Lori A.; Brusic, Vladimir; Zhang, Guanglan; Stern, Joel N. H.

doi:10.1016/j.contre.2022.100015

Cited by 1 publication

(3 citation statements)

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“…Some level of augmentation by LPS was expected given the existing literature that reported the effects of intravesical LPS. [34][35][36][37][38][39][40][41] However, these studies had endpoints different from those of the present study and, in most cases, used different rat strains. A broader search for studies using intravesical LPS as a bladder irritant revealed that the concentrations of LPS required to generate a robust effect in models similar to those used in this study were much higher than the concentrations used in the present study.…”

Section: Discussionmentioning

confidence: 79%

“…20 Central nervous system changes may also explain some of the augmentation of VMRs, as spinal opioidergic and corticotrophinergic mechanisms have been demonstrated to be altered in NBI rats. 32,33 Immunological mechanisms can also be at play within bladder tissues, 34,35 since immune cells express TLR2 and TLR4 and specific populations of B-cells have been noted in subjects with IC/BPS. 34 A concern was that in the present dataset, there was a near-total lack of effects of LPS in NCT rats.…”

Section: Discussionmentioning

confidence: 99%

“…32,33 Immunological mechanisms can also be at play within bladder tissues, 34,35 since immune cells express TLR2 and TLR4 and specific populations of B-cells have been noted in subjects with IC/BPS. 34 A concern was that in the present dataset, there was a near-total lack of effects of LPS in NCT rats. Some level of augmentation by LPS was expected given the existing literature that reported the effects of intravesical LPS.…”

Section: Discussionmentioning

confidence: 99%

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Neonatal Cystitis Makes Adult Female Rat Urinary Bladders More Sensitive to Low Concentration Microbial Antigens

Archer,

DeBerry,

DeWitte

et al. 2023

RRU

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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder. Patients with IC/BPS often experience "flares" of symptom exacerbation throughout their lifetime, initiated by triggers, such as urinary tract infections. This study sought to determine whether neonatal bladder inflammation (NBI) alters the sensitivity of adult rat bladders to microbial antigens. Methods: Female NBI rats received intravesical zymosan treatments on postnatal days P14-P16 while anesthetized; Neonatal Control Treatment (NCT) rats were anesthetized. In adults, bladder and spinal cord Toll-like receptor type 2 and 4 (TLR2, TLR4) contents were determined using ELISAs. Other rats were injected intravesically with lipopolysaccharide (LPS; mimics an E. coli infection; 25, 50, 100, or 200 μg/mL) or Zymosan (mimics yeast infection; 0.01, 0.1, 1, and 10 mg/mL) solutions on the following day. Visceromotor responses (VMRs; abdominal contractions) to graded urinary bladder distention (UBD, 10-60 mm Hg, 20s) were quantified as abdominal electromyograms (EMGs). Results: Bladder TLR2 and TLR4 protein levels increased in NBI rats. These rats displayed statistically significant, dose-dependent, robustly augmented VMRs following all but the lowest doses of LPS and Zymosan tested, when compared with their adult treatment control groups. The NCT groups showed minimal responses to LPS in adults and minimally increased EMG measurements following the highest dose of Zymosan. Conclusion:The microbial antigens LPS and Zymosan augmented nociceptive VMRs to UBD in rats that experienced NBI but had little effect on NCT rats at the doses tested. The greater content of bladder TLR2 and TLR4 proteins in the NBI group was consistent with increased responsiveness to their agonists, Zymosan and LPS, respectively. Given that patients with IC/BPS have a higher incidence of childhood urinary tract infections, this increased responsiveness to microbial antigens may explain the flares in symptoms following "subclinical" tract infections.Plain Language Summary: In a rat model of interstitial cystitis, bladder inflammation during childhood resulted in increased bladder sensitivity (ie, pain) to low-level infections in adults.

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