Vitreous proteomics, a gateway to improved understanding and stratification of diverse uveitis aetiologies
Autor: | Tom Missotten, Nicole M A Nagtzaam, Mirjam E J van Velthoven, Sigrid M. A. Swagemakers, P. Martin van Hagen, P Martijn Kolijn, Peter J. van der Spek, Josianne C E M ten Berge, Anton W. Langerak, Joeri de Hoog, Angelique L. C. T. van Rijswijk, Willem A. Dik, Benjamin Schrijver |
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Přispěvatelé: | Immunology, Ophthalmology, Pathology, Internal Medicine |
Rok vydání: | 2021 |
Předmět: |
Oncology
Proteomics medicine.medical_specialty Tuberculosis Retinal Neoplasms Disease vitreous Uveitis SDG 3 - Good Health and Well-being Intraocular Lymphoma Internal medicine medicine Biomarkers Tumor Humans sarcoidosis business.industry Interleukin-6 Eye Neoplasms Interleukin General Medicine medicine.disease (P)VRL Pathophysiology Interleukin-10 Vitreous Body Ophthalmology tuberculosis Cohort proximity extension assay Sarcoidosis Intraocular lymphoma intraocular business |
Zdroj: | Acta Ophthalmologica, 100(4), 403-413. Wiley-Blackwell Publishing Ltd Acta ophthalmologica. Copenhagen Scriptor |
ISSN: | 1755-3768 1755-375X |
Popis: | Purpose: The vitreous proteome might provide an attractive gateway to discriminate between various uveitis aetiologies and gain novel insights into the underlying pathophysiological processes. Here, we investigated 180 vitreous proteins to discover novel biomarkers and broaden disease insights by comparing (1). primary vitreoretinal lymphoma ((P)VRL) versus other aetiologies, (2). sarcoid uveitis versus tuberculosis (TB)-associated uveitis and (3). granulomatous (sarcoid and TB) uveitis versus other aetiologies. Methods: Vitreous protein levels were determined by proximity extension assay in 47 patients with intraocular inflammation and a prestudy diagnosis (cohort 1; training) and 22 patients with a blinded diagnosis (cohort 2; validation). Differentially expressed proteins identified by t-tests on cohort 1 were used to calculate Youden’s indices. Pathway and network analysis was performed by ingenuity pathway analysis. A random forest classifier was trained to predict the diagnosis of blinded patients. Results: For (P)VRL stratification, the previously reported combined diagnostic value of IL-10 and IL-6 was confirmed. Additionally, CD70 was identified as potential novel marker for (P)VRL. However, the classifier trained on the entire cohort (cohort 1 and 2) relied primarily on the interleukin score for intraocular lymphoma diagnosis (ISOLD) or IL-10/IL-6 ratio and only showed a supportive role for CD70. Furthermore, sarcoid uveitis displayed increased levels of vitreous CCL17 as compared to TB-associated uveitis. Conclusion: We underline the previously reported value of the ISOLD and the IL-10/IL-6 ratio for (P)VRL identification and present CD70 as a potentially valuable target for (P)VRL stratification. Finally, we also show that increased CCL17 levels might help to distinguish sarcoid uveitis from TB-associated uveitis. |
Databáze: | OpenAIRE |
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