Jiang Yuan-Hong, Jhang Jia-Fong, Kuo Hann-Chorng
Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien 43000, Taiwan.
Diagnostics (Basel). 2022 Apr 27;12(5):1093. doi: 10.3390/diagnostics12051093.
Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) has ulcer (HIC) and non-ulcer subtypes. Differentiation of these two subtypes could only be based by cystoscopy. This study analyzed the urinary cytokines and chemokines among IC/BPS subtypes and controls for discriminating HIC from non-HIC and controls. Materials and Methods: A total of 309 consecutive patients with clinically diagnosed IC/BPS were enrolled. All patients received cystoscopic hydrodistention under anesthesia and urine samples were collected prior to the procedure. Enrolled patients were classified into subtypes based on the glomerulation grade, maximal bladder capacity (MBC), and presence of Hunner’s lesion. Inflammation-related cytokines and chemokines in urine samples, including interleukin-8 (IL-8), C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin-1 (eotaxin), IL-6, macrophage inflammatory protein-1 beta (MIP-1β), regulated upon activation, normally T-expressed, and presumably secreted (RANTES), tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) were assayed using commercially available microspheres with the Milliplex® Human Cytokine/Chemokine Magnetic Bead-based Panel kit. The clinical data and urine levels of analytes between IC/BPS patients and controls, and among HIC, non-HIC, and controls were analyzed. Results: Among the 10 proteins, MCP-1, eotaxin, MIP-1β, TNF-α, and PGE2 were significantly different between IC/BPS and control, while IL-8, CXCL10, BDNF, IL-6, and RANTES were significantly higher in HIC than non-HIC patients. The receiver operating characteristic curve was used to analyze each urine biomarker in the patients with IC/BPS and controls. Among the 10 urine biomarkers, MIP-1β and TNF-α had an area under curve of >0.70 to predict IC/BPS from controls, however, the predictive values of these urine biomarkers to predict HIC from non-HIC were low. Combined cut-off values of MIP-1β and TNF-α can only have a 50% sensitivity and 39.6% specificity in identifying HIC from non-HIC. Conclusion: The results of this study demonstrate that urine cytokines and chemokines may be useful to discriminate patients with HIC from controls. An elevation of urine levels of IL-8, CXCL 10, BDNF, IL-6, and RANTES in IC/BPS patients should prompt physicians to consider the diagnosis of HIC.
间质性膀胱炎/膀胱疼痛综合征（IC/BPS）有溃疡型（HIC）和非溃疡型亚型。这两种亚型的区分只能通过膀胱镜检查。本研究分析了IC/BPS各亚型及对照组之间的尿细胞因子和趋化因子，以区分HIC与非HIC及对照组。材料与方法：连续纳入309例临床诊断为IC/BPS的患者。所有患者在麻醉下接受膀胱镜水扩张术，并在手术前采集尿液样本。根据肾小球化分级、最大膀胱容量（MBC）和Hunner病变的存在情况将纳入的患者分为不同亚型。使用基于Milliplex®人细胞因子/趋化因子磁珠板试剂盒的市售微球检测尿液样本中的炎症相关细胞因子和趋化因子，包括白细胞介素-8（IL-8）、C-X-C基序趋化因子配体10（CXCL10）、单核细胞趋化蛋白-1（MCP-1）、脑源性神经营养因子（BDNF）、嗜酸性粒细胞趋化因子-1（嗜酸性粒细胞趋化因子）、IL-6、巨噬细胞炎性蛋白-1β（MIP-1β）、活化后正常T细胞表达并可能分泌的调节蛋白（RANTES）、肿瘤坏死因子-α（TNF-α）和前列腺素E2（PGE2）。分析了IC/BPS患者与对照组之间以及HIC、非HIC和对照组之间的临床数据和分析物尿液水平。结果：在这10种蛋白质中，MCP-1、嗜酸性粒细胞趋化因子、MIP-1β、TNF-α和PGE2在IC/BPS与对照组之间有显著差异，而IL-8、CXCL10、BDNF、IL-6和RANTES在HIC患者中显著高于非HIC患者。采用受试者工作特征曲线分析IC/BPS患者和对照组中的每种尿液生物标志物。在这10种尿液生物标志物中，MIP-1β和TNF-α预测IC/BPS与对照组的曲线下面积>0.70，然而，这些尿液生物标志物预测HIC与非HIC的预测价值较低。MIP-1β和TNF-α的联合临界值在区分HIC与非HIC时的敏感性仅为50%，特异性为39.6%。结论：本研究结果表明，尿细胞因子和趋化因子可能有助于区分HIC患者与对照组。IC/BPS患者尿液中IL-8、CXCL 10、BDNF、IL-6和RANTES水平升高应促使医生考虑HIC的诊断。
