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International Urogynecology Journal

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Open Access 01-12-2013 | Original Article

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

Authors: Marianne Gamper, Volker Viereck, Jakob Eberhard, Jochen Binder, Carlo Moll, JoEllen Welter, René Moser

Published in: International Urogynecology Journal | Issue 12/2013

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.

Harrington DS, Fall M, Johansson SL (1990) Interstitial cystitis: bladder mucosa lymphocyte immunophenotyping and peripheral blood flow cytometry analysis. J Urol 144:868–871PubMed

Johansson SL, Fall M (1990) Clinical features and spectrum of light microscopic changes in interstitial cystitis. J Urol 143:1118–1124PubMed

Hanno PM, Landis JR, Matthews-Cook Y et al (1999) The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database study. J Urol 161:553–557PubMedCrossRef

van de Merwe JP, Nordling J, Bouchelouche P et al (2008) Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol 53:60–67PubMedCrossRef

Gamper M, Viereck V, Geissbühler V et al (2009) Gene expression profile of bladder tissue of patients with ulcerative interstitial cystitis. BMC Genomics 10:199PubMedCrossRef

Slobodov G, Feloney M, Gran C et al (2004) Abnormal expression of molecular markers for bladder impermeability and differentiation in the urothelium of patients with interstitial cystitis. J Urol 171:1554–1558PubMedCrossRef

Zeng Y, Wu XX, Homma Y et al (2007) Uroplakin III-delta4 messenger RNA as a promising marker to identify nonulcerative interstitial cystitis. J Urol 178:1322–1327, discussion 1327PubMedCrossRef

Ogawa T, Homma T, Igawa Y et al (2010) CXCR3 binding chemokine and TNFSF14 over expression in bladder urothelium of patients with ulcerative interstitial cystitis. J Urol 183:1206–1212PubMedCrossRef

Cartwright R, Afshan I, Derpapas A et al (2011) Novel biomarkers for overactive bladder. Nat Rev Urol 8:139–145PubMedCrossRef

10.

Liu HT, Shie JH, Chen SH et al (2012) Differences in mast cell infiltration, E-cadherin, and zonula occludens-1 expression between patients with overactive bladder and interstitial cystitis/bladder pain syndrome. Urology 80(1):225.e13–225.e18CrossRef

11.

Chung SD, Liu HT, Lin H et al (2011) Elevation of serum c-reactive protein in patients with OAB and IC/BPS implies chronic inflammation in the urinary bladder. Neurourol Urodyn 30:417–420PubMedCrossRef

12.

Fluss R, Faraggi D, Reiser B (2005) Estimation of the Youden Index and its associated cutoff point. Biom J 47:458–472PubMedCrossRef

13.

Tyagi P, Killinger K, Tyagi V et al (2012) Urinary chemokines as noninvasive predictors of ulcerative interstitial cystitis. J Urol 187:2243–2248PubMedCrossRef

14.

Blalock EM, Korrect GS, Stromberg AJ et al (2012) Gene expression analysis of urine sediment: evaluation for potential noninvasive markers of interstitial cystitis/bladder pain syndrome. J Urol 187:725–732PubMedCrossRef

15.

Yang W, Kim Y, Kim TK et al (2012) Integration analysis of quantitative proteomics and transcriptomics data identifies potential targets of frizzled-8 protein-related antiproliferative factor in vivo. BJU Int 110:E1138–E1146PubMedCrossRef

16.

Logadottir Y, Hallsberg L, Fall M et al (2013) Bladder pain syndrome/interstitial cystitis ESSIC type 3C: high expression of inducible nitric oxide synthase in inflammatory cells. Scand J Urol 47:52–56PubMedCrossRef

17.

Keay S, Zhang CO, Trifillis AL et al (1997) Urine autoantibodies in interstitial cystitis. J Urol 157:1083–1087PubMedCrossRef

18.

Elliott CS, Payne CK (2012) Interstitial cystitis and the overlap with overactive bladder. Curr Urol Rep 13:319–326PubMedCrossRef

19.

Peeker R, Aldenborg F, Fall M (2000) Complete transurethral resection of ulcers in classic interstitial cystitis. Int Urogynecol J Pelvic Floor Dysfunct 11:290–295PubMedCrossRef

20.

Payne RA, O’Connor RC, Kressin M et al (2009) Endoscopic ablation of Hunner’s lesions in interstitial cystitis patients. Can Urol Assoc J 3:473–477PubMed

21.

Corcoran AT, Yoshimura N, Tyagi V et al (2013) Mapping the cytokine profile of painful bladder syndrome/interstitial cystitis in human bladder and urine specimens. World J Urol 31:241–246PubMedCrossRef

22.

van de Merwe JP (2007) Interstitial cystitis and systemic autoimmune diseases. Nat Clin Pract Urol 4:484–491PubMedCrossRef

23.

Boross P, Leusen JH (2012) Mechanisms of action of CD20 antibodies. Am J Cancer Res 2:676–690PubMed

24.

Edwards JC, Cambridge G (2006) B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 6:394–403PubMedCrossRef

25.

Peeker R, Fall M (2002) Toward a precise definition of interstitial cystitis: further evidence of differences in classic and nonulcer disease. J Urol 167:2470–2472PubMedCrossRef

26.

Erickson DR, Tomaszewski JE, Kunselman AR et al (2008) Urine markers do not predict biopsy findings or presence of bladder ulcers in interstitial cystitis/painful bladder syndrome. J Urol 179:1850–1856PubMedCrossRef

Title: Local immune response in bladder pain syndrome/interstitial cystitis ESSIC type 3C
Authors: Marianne Gamper
Volker Viereck
Jakob Eberhard
Jochen Binder
Carlo Moll
JoEllen Welter
René Moser
Publication date: 01-12-2013
Publisher: Springer London
Published in: International Urogynecology Journal / Issue 12/2013
Print ISSN: 0937-3462
Electronic ISSN: 1433-3023
DOI: https://doi.org/10.1007/s00192-013-2112-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Introduction and hypothesis

Methods

Results

Conclusions

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Springer Medicine

Abstract

Introduction and hypothesis

Methods

Results

Conclusions

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