title: A multiplexed analysis approach identifies new association of inflammatory proteins in patients with overactive bladder.
abstract: Overactive bladder (OAB) is a common debilitating bladder condition with unknown etiology and limited diagnostic modalities. Here, we explored a novel high-throughput and unbiased multiplex approach with cellular and molecular components in a well-characterized patient cohort to identify biomarkers that could be reliably used to distinguish OAB from controls or provide insights into underlying etiology. As a secondary analysis, we determined whether this method could discriminate between OAB and other chronic bladder conditions. We analyzed plasma samples from healthy volunteers (n = 19) and patients diagnosed with OAB, interstitial cystitis/bladder pain syndrome (IC/BPS), or urinary tract infections (UTI; n = 51) for proinflammatory, chemokine, cytokine, angiogenesis, and vascular injury factors using Meso Scale Discovery (MSD) analysis and urinary cytological analysis. Wilcoxon rank-sum tests were used to perform univariate and multivariate comparisons between patient groups (controls, OAB, IC/BPS, and UTI). Multivariate logistic regression models were fit for each MSD analyte on 1) OAB patients and controls, 2) OAB and IC/BPS patients, and 3) OAB and UTI patients. Age, race, and sex were included as independent variables in all multivariate analysis. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic potential of a given analyte. Our findings demonstrate that five analytes, i.e., interleukin 4, TNF-α, macrophage inflammatory protein-1β, serum amyloid A, and Tie2 can reliably differentiate OAB relative to controls and can be used to distinguish OAB from the other conditions. Together, our pilot study suggests a molecular imbalance in inflammatory proteins may contribute to OAB pathogenesis.
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Emily
authors.initials: E
authors.lastname: Ma
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri; and.
authors.forename: Joel
authors.initials: J
authors.lastname: Vetter
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Laura
authors.initials: L
authors.lastname: Bliss
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri; and Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: H Henry
authors.initials: HH
authors.lastname: Lai
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Indira U
authors.initials: IU
authors.lastname: Mysorekar
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri; Renal Division, Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; jains@dom.wustl.edu.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Jain
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000235:genetics; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D063369:Knowledge Discovery; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D010865:Pilot Projects; D012372:ROC Curve; D014409:Tumor Necrosis Factor-alpha; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D014570:Urologic Diseases / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha
keywords: OAB; UTI; biomarkers; bladder pain syndrome; interstitial cystitis