Local immune response in bladder pain syndrome/interstitial cystitis ESSIC type 3C

Marianne Gamper, Volker Viereck, Jakob Eberhard, Jochen Binder, Carlo Moll, Joellen Welter, René Moser, Marianne Gamper, Volker Viereck, Jakob Eberhard, Jochen Binder, Carlo Moll, Joellen Welter, René Moser

Abstract

Introduction and hypothesis: Bladder pain syndrome/interstitial cystitis (BPS/IC) is identified based on subjective symptoms which lead to heterogeneous patient populations. Previous studies using gene expression arrays for BPS/IC with Hunner's lesions [European Society for the Study of Interstitial Cystitis (ESSIC) type 3C], a subtype of the condition discernible by cystoscopy, have revealed characteristic immune responses and urothelial abnormalities. This current study aimed to further characterize this subtype using a gene expression panel. We hypothesized that B-cell activation with high levels of urinary antibody concentration would be found.

Methods: Cold-cup bladder biopsies, catheterized urine and blood were collected from 15 BPS/IC ESSIC type 3C patients, 11 non-inflammatory overactive bladder (OAB) patients and eight healthy controls. Gene expression in biopsies was quantified by real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry was performed on bladder tissue and urinary immunoglobulins G and A were quantified by enzyme-linked immunosorbent assay. Statistical analyses included the Kruskal-Wallis test for non-parametric data and post hoc tests identified differences between groups.

Results: High expression of T- and B-cell markers (CTLA4, CD20, CD79A, IGH@), low expression of urothelial markers (KRT20, UPK1B, UPK3A), focal lymphoid aggregates in the submucosa and high immunoglobulin concentration in urine were found exclusively in BPS/IC ESSIC type 3C patients. Results for OAB were in intermediate ranges between the other two groups and UPK1B even reached significantly lower expression when compared to healthy controls.

Conclusions: BPS/IC ESSIC type 3C is characterized by a local adaptive immune response with elevated urinary antibody concentrations. Quantification of urinary immunoglobulin levels could be used for a non-invasive diagnosis of BPS/IC ESSIC type 3C.

Figures

Fig. 1
Fig. 1
B- and T-lymphocyte staining in bladder submucosa. Immunohistochemistry with paraffin sections of bladder biopsies using primary monoclonal antibodies against CD4 (T-cell marker) and CD79A (B-cell marker). Representative pictures are shown for the three investigated groups, BPS/IC ESSIC type 3C (group 1), OAB (group 2) and healthy controls (group 3). The respective CD79A and CD4 stainings are from the same biopsy location. All pictures are at the same magnification. The lymphocyte aggregate shown has a size of 100 μm × 170 μm and lymphocyte counts of approximately 200 cells; this results in a lymphocyte density of 1.2 × 104 cells/mm2
Fig. 2
Fig. 2
Staining of urothelium-specific proteins in bladder biopsies. Immunohistochemistry with paraffin sections of bladder biopsies using primary monoclonal antibodies against two urothelial markers, UPK3 (uroplakin 3) and KRT20 (cytokeratin 20). Representative pictures are shown for the three investigated groups, BPS/IC ESSIC type 3C (group 1), OAB (group 2) and healthy controls (group 3). The respective UPK3 and KRT20 stainings are from the same biopsy location. All pictures are at the same magnification

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