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MxA Gene Expression Analysis as an Interferon-β Bioactivity Measurement in Patients with Multiple Sclerosis and the Identification of Antibody-Mediated Decreased Bioactivity

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Abstract

Background: Interferon-β (IFNβ) has proven to be an important advance in the therapy of multiple sclerosis (MS), but optimal markers for bioactivity have not been identified. To accurately measure bioactivity in MS patients treated with IFNβ, we developed and tested a real-time reverse transcriptase (RT)-PCR assay for gene expression of MxA, an IFNβ-induced gene in the peripheral blood of patients treated with IFNβ.

Methods: We compared IFNβ-treated patients with MS to controls in expression of MxA relative to the house-keeping gene, GAPDH. 2′-5′oligoadenylate synthetase (OAS) gene expression was also tested by real-time RT-PCR on RNA from the same patient specimens. Anti-IFNβ antibody was measured by ELISA and a cytopathic effect assay.

Results: Seven of 54 patients were found to have complete loss of bioactivity. MxA expression correlated well with OAS expression. All patients with lost bioactivity had high levels of binding antibodies or neutralizing antibodies.

Conclusions: This is the first demonstration that a real-time RT-PCR assay can be used to monitor therapy with interferons. These data identify MxA mRNA as an excellent biomarker for INFβ action on the IFN receptor, and clarify the relationship between anti-IFNβ antibodies and bioactivity in patients with MS treated with IFNβ.

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Acknowledgements

This study was funded by the Foundation of the University of Medicine and Dentistry of New Jersey through a generous gift from a patient with multiple sclerosis. There are no potential conflicts to disclose.

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Authors and Affiliations

  1. Department of Neurosciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 S. Orange Ave, Newark, New Jersey, 08540, USA

    Andrew R. Pachner, Kavitha Narayan, Nicholson Price, Marie Hurd & Donna Dail

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  1. Andrew R. Pachner
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  2. Kavitha Narayan
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  3. Nicholson Price
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  5. Donna Dail
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Correspondence to Andrew R. Pachner.

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Pachner, A.R., Narayan, K., Price, N. et al. MxA Gene Expression Analysis as an Interferon-β Bioactivity Measurement in Patients with Multiple Sclerosis and the Identification of Antibody-Mediated Decreased Bioactivity. CNS Drugs 7, 17–25 (2003). https://doi.org/10.1007/BF03260016

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