title: Local immune response in bladder pain syndrome/interstitial cystitis ESSIC type 3C.
abstract: OBJECTIVE
  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.
authors.affiliation: IKBT, Institut für Klinische Biomedizinische Forschung Thurgau, Lauchefeld 31, 9548, Matzingen, Switzerland, marianne.gamper@stgag.ch.
authors.forename: Marianne
authors.initials: M
authors.lastname: Gamper
authors.forename: Volker
authors.initials: V
authors.lastname: Viereck
authors.forename: Jakob
authors.initials: J
authors.lastname: Eberhard
authors.forename: Jochen
authors.initials: J
authors.lastname: Binder
authors.forename: Carlo
authors.initials: C
authors.lastname: Moll
authors.forename: Joellen
authors.initials: J
authors.lastname: Welter
authors.forename: René
authors.initials: R
authors.lastname: Moser
mesh_terms: D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000235:genetics; D001402:B-Lymphocytes / Q000502:physiology; D015415:Biomarkers / Q000032:analysis / Q000652:urine; D015496:CD4-Positive T-Lymphocytes; D051925:CD79 Antigens / Q000235:genetics; D060908:CTLA-4 Antigen / Q000235:genetics; D018856:Cystitis, Interstitial / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D005260:Female; D015870:Gene Expression; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood / Q000652:urine*; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood / Q000652:urine*; D053554:Keratin-20 / Q000032:analysis / Q000235:genetics; D008213:Lymphocyte Activation; D008875:Middle Aged; D001743:Urinary Bladder / Q000737:chemistry* / Q000473:pathology*; D053201:Urinary Bladder, Overactive / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D060171:Uroplakin III / Q000032:analysis / Q000235:genetics; D060169:Uroplakin Ib / Q000032:analysis / Q000235:genetics
chemical_list: D018951:Antigens, CD20; D015415:Biomarkers; D051925:CD79 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C507499:KRT20 protein, human; D053554:Keratin-20; C086452:UPK1B protein, human; C554660:UPK3A protein, human; D060171:Uroplakin III; D060169:Uroplakin Ib