Local immune response in bladder pain syndrome/interstitial cystitis ESSIC type 3C.
Local immune response in bladder pain syndrome/interstitial cystitis ESSIC type 3C.
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DOI：
10.1007/s00192-013-2112-0
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发表时间：
2013-12
影响因子：
1.8
通讯作者：
Moser, Rene
中科院分区：
文献类型：
--
作者：
Gamper, Marianne;Viereck, Volker;Eberhard, Jakob;Binder, Jochen;Moll, Carlo;Welter, JoEllen;Moser, Rene
关键词：
膀胱疼痛综合征/间质性膀胱炎（BPS/IC）是根据导致患者人群异质性的主观症状确定的。先前使用基因表达阵列对BPS/IC伴Hunner病变[欧洲间质性膀胱炎研究学会（ESSIC）3C型]（膀胱镜检查可辨别的一种亚型）进行的研究显示了特征性免疫反应和尿路上皮异常。本研究旨在使用基因表达面板进一步表征该亚型。我们假设，B细胞活化与高水平的尿抗体concentration. Cold杯膀胱活检，导尿管的尿液和血液收集15 BPS/IC ESSIC型3C患者，11非炎症性膀胱过度活动症（OAB）患者和8名健康对照。通过实时定量聚合酶链反应（RT-qPCR）定量活检组织中的基因表达，对膀胱组织进行免疫组织化学，并通过酶联免疫吸附试验定量尿免疫球蛋白G和A。统计分析包括非参数数据的Kruskal-Wallis检验和确定组间差异的事后检验。在BPS/IC ESSIC 3C型患者中发现T细胞和B细胞标记物（CTLA 4、CD 20、CD 79 A、IGH）的高表达，尿路上皮标记物（KRT 20、UPK 1B、UPK 3A）的低表达，粘膜下层中的局灶性淋巴样聚集物和尿中的高免疫球蛋白浓度。OAB的结果在其他两组之间的中间范围内，与健康对照相比，UPK 1B甚至达到显著更低的表达。BPS/IC ESSIC 3C型的特征是局部适应性免疫应答，尿抗体浓度升高。尿免疫球蛋白定量可用于BPS/IC ESSIC 3C型的无创性诊断。
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. 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. 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. 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.
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