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Identification of biomarker candidates for exfoliative glaucoma from autoimmunity profiling
University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Sahlgrenska Academy, Gothenburg University, Sweden. (Infektionsbiologi, Infection Biology)
Skaraborgs Sjukhus, Skövde, Sweden ; Karolinska Institutet: Stockholm, Sweden ; Sahlgrenska Academy, Gothenburg University, Sweden.
University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. (Infektionsbiologi, Infection Biology)ORCID iD: 0000-0003-3747-5950
2024 (English)In: BMC Ophthalmology, E-ISSN 1471-2415, Vol. 24, no 1, article id 44Article in journal (Refereed) Published
Abstract [en]

Background: Exfoliative glaucoma (XFG) is a subtype of open-angle glaucoma characterized by distinctive extracellular fibrils and a yet unknown pathogenesis potentially involving immune-related factors. The aim of this exploratory study was to identify biomarkers for XFG using data from autoimmunity profiling performed on blood samples from a Scandinavian cohort of patients. Methods: Autoantibody screening was analyzed against 258 different protein fragments in blood samples taken from 30 patients diagnosed with XFG and 30 healthy donors. The 258 protein fragments were selected based on a preliminary study performed on 3072 randomly selected antigens and antigens associated with the eye. The “limma” package was used to perform moderated t-tests on the proteomic data to identify differentially expressed reactivity between the groups. Results: Multiple associated genes were highlighted as possible biomarker candidates including FUT2, CDH5, and the LOX family genes. Using seven variables, our binary logistic regression model was able to classify the cases from the controls with an AUC of 0.85, and our reduced model using only one variable corresponding to the FUT2 gene provided an AUC of 0.75, based on LOOCV. Furthermore, over-representation gene analysis was performed to identify pathways that were associated with antigens differentially bound to self-antibodies. This highlighted the enrichment of pathways related to collagen fibril formation and the regulatory molecules mir-3176 and mir-876-5p. Conclusions: This study suggests several potential biomarkers that may be useful in developing further models of the pathology of XFG. In particular, CDH5, FUT2, and the LOX family seem to have a relationship which merits additional exploration. 

Place, publisher, year, edition, pages
BioMed Central (BMC), 2024. Vol. 24, no 1, article id 44
Keywords [en]
Autoimmunity, Biomarkers, Exfoliation, Genes, Glaucoma
National Category
Ophthalmology Medical Genetics Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Bioinformatics and Systems Biology
Research subject
Infection Biology
Identifiers
URN: urn:nbn:se:his:diva-23583DOI: 10.1186/s12886-024-03314-yISI: 001153831500002PubMedID: 38287276Scopus ID: 2-s2.0-85183441039OAI: oai:DiVA.org:his-23583DiVA, id: diva2:1836037
Funder
University of Gothenburg
Note

CC BY 4.0 DEED

© 2024, The Author(s).

Correspondence Address: R. Potter; Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; email: ryan.potter@his.se

Open access funding provided by University of Gothenburg. This study was funded by Synskadades Vänner Skaraborg (SVS).

Available from: 2024-02-08 Created: 2024-02-08 Last updated: 2024-04-15Bibliographically approved

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Potter, RyanTilevik, Andreas

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