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Screening for Circulating Inflammatory Proteins Does Not Reveal Plasma Biomarkers of Constant Tinnitus
Section of Experimental Audiology, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Ropewalk House, Nottingham, UK, Ropewalk House; Department of Otolaryngology, Head and Neck Surgery, Translational Hearing Research, Tübingen Hearing Research Center, University of Tübingen, Tubingen, Germany.
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. Department of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Stockholm University, Stockholm, Sweden.ORCID iD: 0000-0001-8603-8293
Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College London, London, UK.
Section of Experimental Audiology, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
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2023 (English)In: Journal of the Association for Research in Otolaryngology, ISSN 1525-3961, E-ISSN 1438-7573, Vol. 24, no 6, p. 593-606Article in journal (Refereed) Published
Abstract [en]

Background and Objective: Tinnitus would benefit from an objective biomarker. The goal of this study is to identify plasma biomarkers of constant and chronic tinnitus among selected circulating inflammatory proteins. Methods: A case–control retrospective study on 548 cases with constant tinnitus and 548 matched controls from the Swedish Tinnitus Outreach Project (STOP), whose plasma samples were examined using Olink’s Inflammatory panel. Replication and meta-analysis were performed using the same method on samples from the TwinsUK cohort. Participants from LifeGene, whose blood was collected in Stockholm and Umeå, were recruited to STOP for a tinnitus subtyping study. An age and sex matching was performed at the individual level. TwinsUK participants (n = 928) were selected based on self-reported tinnitus status over 2 to 10 years. Primary outcomes include normalized levels for 96 circulating proteins, which were used as an index test. No reference standard was available in this study. Results: After adjustment for age, sex, BMI, smoking, hearing loss, and laboratory site, the top proteins identified were FGF-21, MCP4, GDNF, CXCL9, and MCP-1; however, these were no longer statistically significant after correction for multiple testing. Stratification by sex did not yield any significant associations. Similarly, associations with hearing loss or other tinnitus-related comorbidities such as stress, anxiety, depression, hyperacusis, temporomandibular joint disorders, and headache did not yield any significant associations. Analysis in the TwinsUK failed in replicating the top candidates. Meta-analysis of STOP and TwinsUK did not reveal any significant association. Using elastic net regularization, models exhibited poor predictive capacity tinnitus based on inflammatory markers [sensitivity = 0.52 (95% CI 0.47–0.57), specificity = 0.53 (0.48–0.58), positive predictive value = 0.52 (0.47–0.56), negative predictive values = 0.53 (0.49–0.58), and AUC = 0.53 (0.49–0.56)]. Discussion: Our results did not identify significant associations of the selected inflammatory proteins with constant tinnitus. Future studies examining longitudinal relations among those with more severe tinnitus and using more recent expanded proteomics platforms and sampling of cerebrospinal fluid could increase the likelihood of identifying relevant molecular biomarkers.

Place, publisher, year, edition, pages
Springer Nature , 2023. Vol. 24, no 6, p. 593-606
Keywords [en]
Auditory, Biomarker, Constant, Diagnostic, Olink, Plasma, Profiling, Tinnitus
National Category
Medical and Health Sciences
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URN: urn:nbn:se:kth:diva-348554DOI: 10.1007/s10162-023-00920-3ISI: 001120195000002PubMedID: 38079022Scopus ID: 2-s2.0-85179308939OAI: oai:DiVA.org:kth-348554DiVA, id: diva2:1880528
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QC 20240701

Available from: 2024-07-01 Created: 2024-07-01 Last updated: 2024-07-01Bibliographically approved

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Hong, Mun-GwanSchwenk, Jochen M.

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