Natalizumab-induced POU2AF1/Spi-B upregulation: A possible route for PML development

Meira, Maria and Sievers, Claudia and Hoffmann, Francine and Haghikia, Aiden and Rasenack, Maria and Decard, Bernhard F. and Kuhle, Jens and Derfuss, Tobias and Kappos, Ludwig and Lindberg, Raija L.P.. (2016) Natalizumab-induced POU2AF1/Spi-B upregulation: A possible route for PML development. Neurol Neuroimmunol Neuroinflamm, 3 (3). e223.

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Official URL: https://edoc.unibas.ch/61666/

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OBJECTIVES: To assess messenger RNA (mRNA) expression of POU2AF1 and Spi-B and their potential regulatory microRNAs (miRNAs) in natalizumab-treated patients with multiple sclerosis and in therapy-associated progressive multifocal leukoencephalopathy (PML). METHODS: Expression of POU2AF1/Spi-B was analyzed by using real-time reverse transcription PCR assays on isolated B/CD8(+) T lymphocytes and peripheral blood mononuclear cells (PBMCs) from cohorts of untreated and natalizumab-treated patients with and without PML. Longitudinal expression analysis was performed on CD4(+), CD8(+) T and B cells from 14 patients who interrupted natalizumab therapy for 8 weeks. The miRNA profiling was conducted in PBMCs from 5 untreated and 5 natalizumab-treated patients using low-density arrays followed by validation with single miRNAs assays in untreated and natalizumab-treated patients. RESULTS: POU2AF1 and Spi-B mRNAs were upregulated in B and CD8(+) T cells from natalizumab-treated patients, which was validated in PBMCs from different cohorts of natalizumab-treated patients with and without PML, with a noteworthy higher expression of Spi-B in patients with PML. In contrast, downregulation of POU2AF1/Spi-B expression was measured in B and CD8(+) T cells after natalizumab discontinuation. Seventeen differentially expressed miRNAs including miR-10b, a regulator of POU2AF1 mRNA, were identified in long-term natalizumab-treated patients compared with untreated ones. CONCLUSIONS: Upregulation of POU2AF1 and Spi-B, known transactivators of the JC virus, the causative agent for PML, and its association with occurrence of PML in natalizumab-treated patients, corroborates POU2AF1/Spi-B as potential biomarkers for PML risk, which merits further evaluation.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Clinical Neuroimmunology (Derfuss/Lindberg)
UniBasel Contributors:Derfuss, Tobias Johannes and Lindberg Gasser, Raija L.P.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wolters Kluwer Health
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Jul 2020 12:37
Deposited On:21 Jul 2020 12:37

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